title: Usain Bolt

text: In 2017, the Jamaican team was stripped of the 2008 Olympics 4×100 metre title due to Nesta Carter's disqualification for doping offences. Bolt, who never failed a dope test, was quoted by the BBC saying that the prospect of having to return the gold was "heartbreaking". The banned substance in Carter's test was identified as methylhexanamine, a nasal decongestant sometimes used in dietary supplements.


title: Usain Bolt

text: At the 2017 World Athletics Championships, Bolt won his heat uncomfortably after a slow start in 10.07, in his semi-final he improved to 9.98 but was beaten by Christian Coleman by 0.01. That race broke Bolt's 4 year winning streak in the 100 m. In his final individual race, in the final, Bolt won the bronze medal in 9.95, 0.01 behind silver medalist Coleman and 0.03 behind World Champion Justin Gatlin. It was the first time Bolt had been beaten at a major championship since the 4×100 m relay of the 2007 World Athletics Championships. Also at the 2017 World Athletics Championships, Bolt participated as the anchor runner for Jamaica's 4×100-metre relay team in both the heats and the final. Jamaica won their heat comfortably in 37.95 seconds. In what was intended to be his final race, Bolt pulled up in agony with 50 metres to go and collapsed to the track after what was later confirmed to be another hamstring injury. He refused a wheelchair and crossed the finish line one last time with the assistance of his teammates Omar McLeod, Julian Forte, and Yohan Blake.


title: Usain Bolt

text: Following his 2017 season, Bolt had a statue of him unveiled in his honour at the National Stadium in Kingston on 3 December 2017. The statue shows him in his signature "lightning bolt" pose.


title: Usain Bolt

text: Bolt expresses a love for dancing and his character is frequently described as laid-back and relaxed. His Jamaican track and field idols include Herb McKenley and former Jamaican 100 m and 200 m world record holder Don Quarrie. Michael Johnson, the former 200 m world and Olympic record holder, is also held in high esteem by Bolt.


title: Usain Bolt

text: Bolt has the nickname "Lightning Bolt" due to his name and speed. He is Catholic and known for making the sign of the cross before racing competitively, and he wears a Miraculous Medal during his races. His middle name is St. Leo.


title: Usain Bolt

text: In 2010, Bolt also revealed his fondness of music, when he played a reggae DJ set to a crowd in Paris. He is also an avid fan of the "Call of Duty" video game series, saying, "I stay up late [playing the game online], I can't help it."


title: Usain Bolt

text: In his autobiography, Bolt reveals that he has suffered from scoliosis, a condition that has curved his spine to the right and has made his right leg shorter than his left. A result of this is that his left leg remains on the ground 14 percent longer than his right leg, with left leg striking the ground with a force of and right with . Biomechanics researchers have studied, with no firm conclusions, whether this asymmetry has helped or hurt Bolt in his sprinting career.


title: Usain Bolt

text: He popularised the "lightning bolt" pose, also known as "to di world" or "bolting", which he used both before races and in celebration. The pose consists of extending a slightly raised left arm to the side and the right arm folded across the chest, with both hands have the thumb and index finger outstretched. His performance of the pose during his Olympic and World Championship victories led to widespread copying of the move, from American President Barack Obama to small children. It has been suggested that the pose comes from Jamaican dancehall moves of the period, though Olympic sprint champion Bernard Williams also had performed similar celebration moves earlier that decade. His habit of fist bumping the volunteers for good luck has been noted in the media.


title: Usain Bolt

text: In 2021, Bolt told the BBC that his love for video games, such as Mario Kart and Mortal Kombat, helped him during his Olympic career.


title: Usain Bolt

text: On 17 May 2020, Bolt's longtime girlfriend Kasi Bennett gave birth to their first child, a daughter named Olympia Lightning Bolt. Bolt and Bennett welcomed twin boys named Saint Leo and Thunder in June 2021.


title: Usain Bolt

text: Cricket was the first sport to interest Bolt, and he said if he were not a sprinter, he would be a fast bowler instead. As a child, he admired the bowling of Waqar Younis. He is also a fan of Indian batsman Sachin Tendulkar, West Indian opener Chris Gayle, and Australian opener Matthew Hayden. During a charity cricket match, Bolt clean-bowled Gayle who was complimentary of Bolt's pace and swing. Bolt also struck a six off Gayle's bowling. Another bowler complimentary of Bolt's pace was former West Indies fast-bowling great Curtly Ambrose.


title: Usain Bolt

text: After talking with Australian cricketer Shane Warne, Bolt suggested that if he were able to get time off he would be interested in playing in the cricket Big Bash League. Melbourne Stars chief executive Clint Cooper said there were free spots on his team should be available. Bolt stated that he enjoyed the Twenty20 version of the game, admiring the aggressive and constant nature of the batting. On his own ability, he said "I don't know how good I am. I will probably have to get a lot of practice in."


title: Usain Bolt

text: Bolt is also a fan of Premier League football team Manchester United. He has declared he is a fan of Dutch striker Ruud van Nistelrooy. Bolt was a special guest of Manchester United at the 2011 UEFA Champions League Final in London, where he stated that he would like to play for them after his retirement.


title: Usain Bolt

text: In 2013, Bolt played basketball in the NBA All-Star Weekend Celebrity Game. He scored two points from a slam dunk but acknowledged his other basketball skills were lacking.


title: Usain Bolt

text: In an interview with Decca Aitkenhead of "The Guardian" in November 2016, Bolt said he wished to play as a professional footballer after retiring from track and field. He reiterated his desire to play for Manchester United if given a chance and added, "For me, if I could get to play for Manchester United, that would be like a dream come true. Yes, that would be epic."


title: Usain Bolt

text: In 2018, after training with Norwegian side Strømsgodset, Bolt played for the club as a forward in a friendly match against the Norway national under-19 team. He wore the number "9.58" in allusion to his 100 m world record. Bolt wore the same number whilst captaining the World XI during Soccer Aid 2018 at Old Trafford.


title: Usain Bolt

text: On 21 August 2018, on his 32nd birthday, Bolt started training with Australian club Central Coast Mariners of the A-League. He made his friendly debut for the club as a substitute on 31 August 2018 against a Central Coast Select team, made up of players playing in the local area. On 12 October, he started in a friendly against amateur club Macarthur South West United and scored two goals, both in the second half, with his goal celebration featuring his signature "To Di World" pose.


title: Usain Bolt

text: Bolt was offered a two-year contract from Maltese club Valletta, which he turned down on 18 October 2018. On 21 October 2018, Bolt was offered a contract by the Mariners. The Australian FA was helping the Mariners to fund it. Later that month, Perth Glory forward Andy Keogh was critical of Bolt's ability, stating his first touch is "like a trampoline." He added Bolt has "shown a bit of potential but it's a little bit of a kick in the teeth to the professionals that are in the league."


title: Usain Bolt

text: Bolt left the Mariners in early November 2018 after 8 weeks with the club. In January 2019, Bolt decided not to pursue a career in football, saying his "sports life is over."


title: Usain Bolt

text: Bolt, a Green Bay Packers fan, stated in July 2021 he could have considered a career as a wide receiver in the National Football League had the rules on violent tackles related to concussions been as tightly regulated 'back in the day' as they were by that stage. If he had switched to gridiron football, his concern was that he would have been a high-priced target for very heavy hits which made him back out of his desire to try the sport. He also felt certain that even at 34 and being retired he would comfortably be the fastest player in the league.


title: Usain Bolt

text: A documentary film based on the athletic life of Bolt to win three Olympic gold medals, titled "I Am Bolt", was released on 28 November 2016 in United Kingdom. The film was directed by Benjamin Turner and Gabe Turner.


title: Usain Bolt

text: On 24 August 2020, Bolt tested positive for COVID-19 and subsequently went into self-isolation in his home. He said that he was asymptomatic. Bolt had himself tested on 22 August, the day after celebrating his 34th birthday with a party where guests did not wear face masks. Coincidentally, the guests at the party danced in an open field to Jamaican reggae singer Koffee's song "Lockdown".


title: Usain Bolt

text: After winning the 200 m title in the 2002 World Junior Championships in Kingston, Bolt signed a sponsorship deal with Puma. To promote Bolt's chase for Olympic glory in the 2008 Summer Olympics in Beijing, China, Puma released a series of videos including Bolt's then-world-record-setting run in Icahn Stadium and his Olympic preparations. After his record-breaking run in New York City, which was preceded by a lightning storm, the press frequently made puns on the Jamaican's name, nicknaming him "Lightning Bolt" and the "Bolt from the blue". During the 2008 Beijing 100 m final, Bolt wore golden Puma Complete Theseus spikes that had "Beijing 100 m Gold" emblazoned across them. Writing of Bolt's performance at the Olympics, "The Associated Press" said:


title: Usain Bolt

text: In September 2010, Bolt travelled to Australia where his sponsor Gatorade was holding an event called the "Gatorade Bolt" to find Australia's fastest footballer. The event was held at the Sydney International Athletic Centre and featured football players from rugby league, rugby union, Australian rules football, and association football. Prior to the race Bolt gave the runners some private coaching and also participated in the 10th anniversary celebrations for the 2000 Summer Olympic Games.


title: Usain Bolt

text: In January 2012, Bolt impersonated Richard Branson in an advertising campaign for Virgin Media. The campaign was directed by Seth Gordon and features the Virgin founder Branson to promote its broadband service. In March 2012, Bolt starred in an advert for Visa and the 2012 Summer Olympics. In July 2012, Bolt and RockLive launched "Bolt!", an Apple iOS game based on his exploits. "Bolt!" quickly became the No. 1 app in Jamaica and climbed the UK iTunes charts to reach No. 2 on the list of Top Free Apps.


title: Usain Bolt

text: In 2012, Bolt collaborated with headphone maker Soul Electronics to design his own line of headphones. Bolt designed both an in-ear bud and over-ear model with the Jamaican color scheme and his signature "To Di World" pose.


title: Usain Bolt

text: Bolt's autobiography, "My Story: 9.58: Being the World's Fastest Man", was released in 2010. Bolt had previously said that the book "...should be exciting, it's my life, and I'm a cool and exciting guy." His athletics agent is PACE Sports Management.


title: Usain Bolt

text: As part of his sponsorship deal with Puma, the manufacturer sends sporting equipment to his alma mater, William Knibb Memorial High School, every year. At Bolt's insistence, advertisements featuring him are filmed in Jamaica, by a Jamaican production crew, in an attempt to boost local enterprise and gain exposure for the country. In 2017, Bolt had the third highest earning social media income for sponsors among sportspeople (behind Cristiano Ronaldo and Neymar), and he was the only non-footballer in the top seven.


title: Usain Bolt

text: Bolt is the highest paid athlete in the history of the sport. In 2016, Bolt earned about $33 million in one year putting him at No. 32 on Forbes list of "The World's Highest-paid Athletes" making him the only track and field athlete on the list.


title: Usain Bolt

text: Usain Bolt co-founded electric scooter company Bolt Mobility in 2018, created in his namesake. Bolt founded the micromobility company, which provides electric scooters and other yet-to-be released mobility devices, such as the company's upcoming "Bolt Nano". Bolt appeared in Bolt Mobility's debut commercial, released through YouTube and his official Facebook account. Bolt appeared in a number of interviews for the company, alongside CEO Sarah Pishevar Haynes. Bolt made his first public appearance for the company in March 2019, during the company's New York City launch and in CNBC interviews on the NYSE.


title: Usain Bolt

text: In May 2019, the company expanded its services to Europe, introducing the product first in Paris.<br>


title: Usain Bolt

text: In May 2019, Bolt spoke in Paris at the Viva Technology conference, where he introduced the company's future release of the "Nano" minicar. He also met with French president Emmanuel Macron while at the conference. While in France, Bolt participated in a CNN interview where he revealed his reasons for founding the company. Bolt argues that his scooter is different, which allows bag, shopping and mobile phone storage. The scooters have capabilities to reach up to 30 MPH, but are typically capped at 15 MPH depending on city regulation. The company has begun operations in a number of U.S. cities, and plans to expand throughout Europe and Asia.


title: Usain Bolt

text: In early July 2022, Bolt Mobility abruptly ceased operations, leaving bike-sharing programs up in the air, including Burlington, Vermont; Portland, Oregon; Richmond, California; and Richmond, Virginia.


title: Usain Bolt

text: In July 2019, Bolt made his debut as a dancehall music producer with the release of the "Olympe Rosé" riddim that featured 5 tracks from Jamaican dancehall artistes: Dexta Daps "Big Moves", Munga Honorable "Weekend", Christopher Martin "Dweet", Ding Dong "Top A Di Top" and football player turned artist Ricardo "Bibi" Gardner "Mount A Gyal".


title: Usain Bolt

text: In November 2019, he followed up with another compilation called "Immortal Riddim" that included tracks from Vybz Kartel, Masicka, Munga Honorable and Christopher Martin.


title: Usain Bolt

text: In early January 2021, Bolt released a single titled "Living the Dream" with his childhood friend and manager Nugent 'NJ' Walker.


title: Usain Bolt

text: Bolt made a cameo appearance in the opening sketch of 13 October 2012 broadcast of "Saturday Night Live", hosted by Christina Applegate. The segment was a parody of the Vice Presidential debate between Joe Biden and Paul Ryan. In the sketch, Taran Killam mimicking Ryan had just lied about running a 2:50 marathon, a sub-4-minute mile on no training and winning the 100 metres in London when Bolt was introduced as his partner to confirm.


title: Usain Bolt

text: When Ryan asked Bolt "Who won the 100 metres?" the Jamaican gold-medallist answered simply. "I did." Ryan followed up by asking Bolt about his (Ryan's) finish. "You didn't finish. You weren't even there."


title: Usain Bolt

text: In November 2016, Bolt competed against James Corden in a rap battle on the "Drop the Mic" segment of "The Late Late Show with James Corden", which he won.


title: Usain Bolt

text: In late October 2020, Bolt starred in the pilot episode of the cartoon "SCRAM!" produced by KidSuper and Puma as a taxi driver.


title: Usain Bolt

text: Bolt's personal best of 9.58 seconds in 2009 in the 100 metres is the fastest ever run. Bolt also holds the second fastest time of 9.63 seconds, the current Olympic record, and set two previous world records in the event. Bolt's personal best of 19.19 s in the 200 metres is the world record. This was recorded at the 2009 World Championships in Athletics in Berlin against a headwind of . This performance broke his previous world record in the event, his 19.30 s clocking in winning the 2008 Olympic 200 metres title.


title: Usain Bolt

text: Bolt has been on three world-record-setting Jamaican relay teams. The first record, 37.10 seconds, was set in winning gold at the 2008 Summer Olympics, although the result was voided in 2017 when the team was disqualified. The second record came at the 2011 World Championships in Athletics, a time of 37.04 seconds. The third world record was set at the 2012 Summer Olympics, a time of 36.84 seconds.


title: Usain Bolt

text: Bolt also holds the 200 metres world teenage best results for the age categories 15 (20.58 s), 16 (20.13 s, former world youth record), 17 (19.93 s) and 18 (19.93 s, world junior record). He also holds the 150 metres world best set in 2009, during which he ran the last 100 metres in 8.70 seconds, the quickest timed 100 metres ever.


title: Usain Bolt

text: Bolt completed a total of 53 wind-legal sub-10-second performances in the 100 m during his career, with his first coming on 3 May 2008 and his last on 5 August 2017 at the World Championships. His longest undefeated streak in the 200 m was in 17 finals, lasting from 12 June 2008 to 3 September 2011. He also had a win-streak covering 14 100 m finals from 16 August 2008 to 16 July 2010.


title: Usain Bolt

text: Bolt claimed 19 Guinness World Records, and, after Michael Phelps, holds the second highest number of accumulative Guinness World Records for total number of accomplishments and victories in sports.


title: Usain Bolt

text: From his record time of 9.58 s for the 100 m sprint, Usain Bolt's average ground speed equates to . However, once his reaction time of 0.148 s is subtracted, his time is 9.44 s, making his average speed . Bolt's top speed, based on his split time of 1.61 s for the 20 metres from the 60- to 80-metre marks (made during the 9.58 WR at 100m), is 12.42 m/s ().


title: Milo Ventimiglia

text: Milo Anthony Ventimiglia (, ; born July 8, 1977) is an American actor. Making his screen acting debut on "The Fresh Prince of Bel-Air" in 1995, he portrayed the lead role on the short-lived series "Opposite Sex" in 2000 before landing his breakthrough role the following year as Jess Mariano on "Gilmore Girls" (2001–2007).


title: Milo Ventimiglia

text: Thereafter, he appeared as Chris Pierce on "American Dreams" (2004–2005) and Richard Thorne on "The Bedford Diaries" (2006) before starring as Peter Petrelli on "Heroes" (2006–2010), for which he received nominations for Teen Choice, Saturn and People's Choice Awards. After appearing in main roles on the series "Mob City" (2013), "Chosen" (2013), and "The Whispers" (2015), Ventimiglia began starring as Jack Pearson on "This Is Us" (2016–2022), for which he has received three nominations for the Primetime Emmy Award for Outstanding Lead Actor in a Drama Series and twice received the Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Drama Series as a cast member.


title: Milo Ventimiglia

text: In film, Ventimiglia made his breakthrough as Rocky Balboa's son in the sixth installment of the "Rocky" film series, "Rocky Balboa" (2006), going on to reprise the role in the eighth installment "Creed II" (2018). He has also appeared in "Pathology" (2008), "That's My Boy" (2012), "Kiss of the Damned" (2013), "Grace of Monaco" (2014), "Devil's Gate" (2017), and "The Art of Racing in the Rain" (2019).


title: Milo Ventimiglia

text: Ventimiglia was born on July 8, 1977 in Anaheim, California, the youngest child of Carol ("née" Wilson) and Peter Ventimiglia, a Vietnam War veteran. He has two sisters, Leslie and Laurel. His father is of Italian-Sicilian descent and his mother is of English and Scottish ancestry. Ventimiglia has a self-described "crooked mouth," having been born with damaged facial nerves causing the left side of his mouth to remain immobile – much like actor Sylvester Stallone, with whom he worked in "Rocky Balboa".


title: Milo Ventimiglia

text: Ventimiglia attended El Modena High School in Orange, California. During high school, Ventimiglia wrestled, acted in drama productions and served as student government president, graduating in 1995. At eighteen, Ventimiglia studied at the American Conservatory Theater for their summer program, subsequently attending the University of California, Los Angeles as a theatre major.


title: Milo Ventimiglia

text: At eighteen, Ventimiglia pursued an acting career, first starring as a gay teenager in "Must Be the Music", a short film released as part of Strand Releasing's "Boys Life 2". He enrolled at UCLA before landing a role on "The Fresh Prince of Bel Air," guest starring on television series including "", "Sabrina, the Teenage Witch", "" and "Boston Public." He played Jed Perry, in the short-lived Fox TV series, "Opposite Sex", which originally aired in 2000.


title: Milo Ventimiglia

text: From 2001 to 2006, Ventimiglia played brooding teen Jess Mariano on "Gilmore Girls"; he was introduced in the second season as a leading cast member. He signed on for a spin-off of "Gilmore Girls" called "Windward Circle" which was to be focused on the relationship between Jess and his estranged father (played by Rob Estes), but the proposed series never made it to air. Afterward, he dropped down to a guest star/recurring cast member, and he came back for four episodes in season four and two episodes in season six. In the third and final season of "American Dreams", Ventimiglia played Chris Pierce, the rebellious boyfriend of Meg Pryor (Brittany Snow); Pierce and his single mother, Shelly (Daphne Zuniga), a Playboy bunny, move into the house next to the Pryors. In 2005, he starred in the mid-season replacement series "The Bedford Diaries". The producers had only Ventimiglia in mind, but the show lasted only eight episodes and was one of several shows not picked up by the newly formed network The CW.


title: Milo Ventimiglia

text: In between television work, Ventimiglia had supporting roles in the horror films "Cursed" (2005), directed by Wes Craven, and "Stay Alive" (2006), as well as starring roles in the short film "Intelligence" and the full-length feature "Dirty Deeds" (2005). The same year, he was cast as Robert "Rocky Jr." Balboa, the son of Rocky Balboa, in the sixth "Rocky" installment "Rocky Balboa" which was released in December 2006.


title: Milo Ventimiglia

text: He starred as Peter Petrelli in the NBC series "Heroes", a show about "ordinary" people discovering they have superpowers, and portrayed the character until the series' conclusion in 2010. Ventimiglia also produced and developed a mini web-series called "It's a Mall World" as part of a marketing campaign for American Eagle Outfitters in 2007. In mid-2007 he starred as the love interest of pop/R&B singer Fergie in the music video for "Big Girls Don't Cry". In 2008, he starred as a medical student in the horror film "Pathology". The movie co-starred "Charmed" actress Alyssa Milano and was directed by Marc Schölermann for MGM.


title: Milo Ventimiglia

text: In 2005, Divide Pictures created the DSC, or Divide Social Club, an online and global social network for like-minded people co-founded by Ventimiglia with his best friends Russ Cundiff and Dino DeMilio, a radio producer for "The Tom Leykis Show". Ventimiglia, Cundiff, and Divide Pictures partnered with Top Cow to produce the comic series REST which will be a monthly limited series. The comic is about John Barrett, a white-collar New Yorker whose life changes when he becomes addicted to a drug that prevents him from falling asleep. Divide also has a comic book called Berserker written by Rick Loverd.


title: Milo Ventimiglia

text: After working with writers Mark Neveldine and Brian Taylor on "Pathology", Ventimiglia appeared in the pair's next film, "Gamer". Ventimiglia also starred in the Xavier Gens apocalypse thriller film, "The Divide".


title: Milo Ventimiglia

text: Ventimiglia was the voice of Wolverine in the English dub of the "Marvel Anime: Wolverine" anime series and reprised his role in an episode of the "Marvel Anime: Iron Man" and an episode of "Marvel Anime: Blade". He did not return to voice Wolverine in "Marvel Anime: X-Men", due to that series portraying an older Wolverine, instead Wolverine was voiced by Steven Blum. He played Ned Stax, a former marine, in Frank Darabont's short-lived neo-noir crime drama "Mob City" for TNT. He also reprised his role as Jess Mariano in "" in November 2016. After this, he reportedly told USA Today that, "I hear rumors that they're bringing back everything that I've ever been a part of... I think it's exciting. At times, though, I think it's too much. There are more stories to tell with a lot of these characters, but at the same time some of these characters for some of us actors are more than a decade in the past. It was exciting going back to Gilmore Girls for the four Netflix movies, but I'm satisfied with it. I think the stories were told. I think it was great for the audience and fans to get just one small taste of that world again. But, at the same time, I think people should not get so greedy."


title: Milo Ventimiglia

text: Beginning in the fall of 2016, Ventimiglia starred opposite Mandy Moore in the critically acclaimed NBC period drama series "This Is Us" playing Jack Pearson, the patriarch of a middle-class family in late 1980s/early 1990s America. Ventimiglia stars in the upcoming suspense thriller "Devil's Gate", alongside Amanda Schull. For his role as Jack Pearson, Ventimiglia received his first Emmy nomination in the category Outstanding Lead Actor in a Drama Series.


title: Milo Ventimiglia

text: In 2019, Ventimiglia starred opposite Amanda Seyfried in the film adaptation of "The Art of Racing in the Rain", based on the novel by Garth Stein.


title: Milo Ventimiglia

text: Ventimiglia and fellow former "Gilmore Girls" co-star Alexis Bledel were in a relationship from 2002 to July 2006. Ventimiglia also dated his "Heroes" co-star Hayden Panettiere from December 2007 to February 2009.


title: Milo Ventimiglia

text: Ventimiglia and his sisters were raised as lacto-vegetarians, and he has maintained the diet as an adult. He was named People for the Ethical Treatment of Animals' Sexiest Vegetarian in 2009. He also does not smoke cigarettes or drink alcohol. He is a fan of The Clash as well as The Smiths and Morrissey.


title: Milo Ventimiglia

text: Ventimiglia took a United Service Organization tour in July 2008, in support of American troops in Kuwait, Iraq and Afghanistan.


title: Jonathan Larson

text: Jonathan David Larson (February 4, 1960 – January 25, 1996) was an American composer, lyricist and playwright most famous for writing the musicals "Rent" and "Tick, Tick... Boom!", which explored the social issues of multiculturalism, substance use disorder, and homophobia. He received three posthumous Tony Awards and a posthumous Pulitzer Prize for Drama for "Rent".


title: Jonathan Larson

text: Larson was born in Mt. Vernon, New York to Nanette ( Notarius) and Allan Larson of White Plains, New York, on February 4, 1960. His family was Jewish. His grandfather, Bernard Isaac Lazarson, who was born in Russia, changed the family surname from Lazarson. At an early age, Larson played the trumpet and tuba, sang in his school's choir, and took piano lessons. His early musical influences and his favorite rock musicians included Elton John, The Doors, The Who, and Billy Joel, as well as the classic composers of musical theatre, especially Stephen Sondheim. He also loved Pete Townshend, The Police, Prince, Liz Phair, and The Beatles. Larson attended White Plains High School, where he was also involved in acting, performing in lead roles in various productions, graduating in 1978. He had a sister, Julie.


title: Jonathan Larson

text: Larson attended Adelphi University in Garden City, New York, with a four-year scholarship as an acting major, in addition to performing in numerous plays and musical theatre, graduating in 1982 with a Bachelor of Fine Arts degree. Larson stopped acting to focus on compositions. During his college years, he began music composition, composing music first for small student productions, called cabarets, and later the score to a musical entitled "The Book of Good Love" ("Libro de Buen Amor"), written by the department head, Jacques Burdick, who was also Larson's college mentor.


title: Jonathan Larson

text: As a student at Adelphi University, Larson co-wrote "Sacrimmoralinority," a Brechtian-themed cabaret musical and his first musical, with David Glenn Armstrong. It was first staged at Adelphi University in the winter of 1981. After Larson and Armstrong graduated in 1982, they renamed it "Saved! - An Immoral Musical on the Moral Majority." It played a four-week showcase run at Rusty's Storefront Blitz, a small theatre on 42nd Street in New York, Manhattan, and won both authors a writing award from ASCAP.


title: Jonathan Larson

text: After graduating, Larson participated in a summer stock theatre program at The Barn Theatre in Augusta, Michigan, as a piano player, which resulted in his earning an Equity card for membership in the Actors' Equity Association.


title: Jonathan Larson

text: In 1983, Larson planned to write a musical adaptation of George Orwell's book "Nineteen Eighty-Four", which he planned to get produced in the year 1984; however, the Orwell estate denied him permission. Larson then began the process of adapting his work on 1984 into a futuristic story of his own, titled "Superbia".


title: Jonathan Larson

text: "Superbia" was modified many times. In the first drafts, the story, set in the year 2064, followed the character Josh Out, a member of OUTLAND, a society where emotions are erased from everyone at birth. Due to complications at birth, Josh maintained his emotions, and spent his life as an inventor, searching for something that could wake up the rest of his family and society. One day, Josh discovers a Music Box, which has the power to bring emotions to the other members of OUTLAND. He meets Elizabeth In, a girl his age from INCITY, who convinces him to spread the power of the music box. Josh travels to INCITY, where the INs live. The INs are the celebrities of this society who spend their days having their scripted lives filmed and transmitted to the OUTs as entertainment. In INCITY, Josh must face the temptations of fame in order to succeed on his mission. By the time Larson finished his final draft of the show, it was a much darker piece that took a deeper look into the power of emotions and mankind's attachment to technology. In this version, Josh was already married to Elizabeth at the beginning of the story and they are both OUTs. Like the other OUTs, Elizabeth is addicted to technology, and is unable to truly love. As the story begins, Josh leaves Elizabeth in order to find a greater life. Elizabeth wakes up from her technological trance and pursues Josh.


title: Jonathan Larson

text: "Superbia" won the Richard Rodgers Production Award and the Richard Rodgers Development Grant. However, despite performances at Playwrights Horizons and a rock concert version produced by Larson's close friend and producer Victoria Leacock at the Village Gate in September 1989, "Superbia" never received a full production.


title: Jonathan Larson

text: In the 2001 three-person musical version of Larson's monologue TICK, TICK... BOOM, the 11 o'clock number from the Musical Comedy version of Superbia, "Come to your Senses" was included. Another song from "Superbia" ("LCD Readout") was included on the 2007 album "Jonathan Sings Larson". In 2019, the song "One of these Days", originally sung by Josh near the beginning of the early drafts of "Superbia", was included on the album "The Jonathan Larson Project".


title: Jonathan Larson

text: On February 4, 2022, "Sextet Montage" was released on streaming platforms as a single, and is currently the only song from "Superbia" available for streaming.


title: Jonathan Larson

text: His next work, completed in 1991, was an autobiographical "rock monologue" entitled "30/90", which was later renamed "Boho Days" and finally titled "Tick, Tick... Boom!" This piece, written for only Larson with a piano and rock band, drew on his feelings of rejection caused by the disappointment of "Superbia". The show was performed off-Broadway at the Village Gate in Greenwich Village, then at the Second Stage Theater on the Upper West Side. Both of these productions were produced by Victoria Leacock. The producer Jeffrey Seller saw a reading of "Boho Days" and expressed interest in producing Larson's musicals. After Larson's death, the work was reworked into a stage musical by playwright David Auburn and arranger and musical director Stephen Oremus. The stage version premiered off-Broadway in 2001 and starred Raúl Esparza as Larson, a performance for which he earned an Obie Award. It has since been produced on a West End theatre. A film adaptation of "tick, tick... BOOM!", directed by Lin-Manuel Miranda and starring Andrew Garfield (in an Academy Award nominated performance) as Larson, with a rewritten script by Steven Levenson was released on Netflix on November 12, 2021.


title: Jonathan Larson

text: In 1992, Larson collaborated with fellow composer/lyricists Rusty Magee, Bob Golden, Paul Scott Goodman, and Jeremy Roberts on "Sacred Cows," which was devised and pitched to television networks as a weekly anthology with each episode taking a different Biblical or mythological story and giving it a '90s celebrity twist. The project was shelved due to scheduling conflicts among the five composers but resurfaced over 20 years later in a six-page "Playbill" article. The demo for "Sacred Cows" was released on iTunes.


title: Jonathan Larson

text: Larson's strongest musical theatre influence was Stephen Sondheim, with whom he corresponded, and to whom he occasionally submitted his work for review. One "tick, tick... BOOM!" song, called "Sunday," is a homage to Sondheim, who supported Larson, staying close to the melody and lyrics of Sondheim's own song of the same title but turning it from a manifesto about art into a waiter's lament. Sondheim wrote several letters of recommendation for Larson to various producers. Larson later won the Stephen Sondheim Award.


title: Jonathan Larson

text: In addition to his three larger theatrical pieces written before "Rent", Larson also wrote music for "J.P. Morgan Saves the Nation"; numerous individual numbers; music for "Sesame Street"; music for the children's book cassettes of "An American Tail" and "The Land Before Time"; music for "Rolling Stone" magazine publisher Jann Wenner; a musical called "Mowgli"; and four songs for the children's video "Away We Go!", which he also conceived with collaborator and composer Bob Golden and directed. He performed in John MacLachlan Gray's musical "Billy Bishop Goes to War", which starred his close friend actor Roger Bart ("Desperate Housewives"). For his early works, Larson won a grant and award from the American Society of Composers, Authors and Publishers and the Gilman & Gonzalez-Falla Theatre Foundation's Commendation Award.


title: Jonathan Larson

text: In 1988, playwright Billy Aronson wanted to create "a musical inspired by Giacomo Puccini's "La bohème", in which the luscious splendor of Puccini's world would be replaced with the coarseness and noise of modern New York".


title: Jonathan Larson

text: In 1989, Aronson called Ira Weitzman, asking for ideas for collaborators, and Weitzman introduced Larson to Aronson to collaborate on the new project. Larson came up with the title and suggested moving the setting from the Upper West Side to Lower Manhattan, where Larson and his roommates lived in a rundown apartment.


title: Jonathan Larson

text: "Rent" started as a staged reading in 1993 at the New York Theatre Workshop, followed by a studio production that played a three-week run a year later. However, the version that is now known worldwide, the result of three years of collaboration and editing between Larson and the producers and director, was not publicly performed before Larson's death as Larson died the day before the first preview performance. The show premiered Off-Broadway on schedule. According to lead performer Anthony Rapp, Larson's parents, who were flying in for the show anyway, gave their blessing to perform the show despite Larson's death a day earlier, and the cast agreed that they would premiere the show by simply singing it through, all the while sitting at three prop tables lined up on stage. But by the time the show got to its high energy "La Vie Boheme", the cast could no longer contain themselves and did the rest of the show as it was meant to be, minus costumes, to the crowd and the Larson family's approval. Once the show was over, there was a long applause followed by silence which was eventually broken when an audience member shouted out "Thank you, Jonathan Larson."


title: Jonathan Larson

text: "Rent" played through its planned engagement to sold-out crowds and was continually extended. The decision was finally made to move the show to a Broadway theatre, and it opened at the Nederlander Theatre on April 29, 1996. In addition to the New York Theatre Workshop, "Rent" was produced by Jeffrey Seller, who was introduced to Larson's work when attending an off-Broadway performance of "Boho Days", and two of his producer friends who also wished to support the work, Kevin McCollum and Allan S. Gordon.


title: Jonathan Larson

text: For his work on "Rent", Larson was posthumously awarded the Pulitzer Prize for Drama, the Tony Award for Best Musical, Tony Award for Best Book of a Musical, and Tony Award for Best Original Score; the Drama Desk Award for Outstanding Book of a Musical, Drama Desk Award for Outstanding Music, and the Drama Desk Award for Outstanding Lyrics; the New York Drama Critics Circle Award for Best Musical; the Outer Critics Circle Award for Best Musical in the Off-Broadway category; and Obie Awards for Outstanding Book, Outstanding Lyrics, and Outstanding Music.


title: Jonathan Larson

text: Larson died at his home in the early morning of January 25, 1996, ten days before his 36th birthday, the day of the first Off-Broadway preview performance of "Rent". An autopsy determined Larson died from an aortic dissection. His body was found on the kitchen floor by his roommate at 3AM. Larson had been suffering severe chest pains, dizziness, and shortness of breath for several days before his death, but doctors at Cabrini Medical Center and St. Vincent's Hospital could not find signs of an aortic dissection even after conducting a chest X-ray and electrocardiogram, so his condition was misdiagnosed as influenza or stress. A court found that Larson "was misdiagnosed at both hospitals" and a medical malpractice lawsuit was settled for an undisclosed amount. New York State medical investigators concluded that Larson may have lived if the aortic dissection had been properly diagnosed and treated with cardiac surgery. It has been speculated that Larson had undiagnosed Marfan syndrome, a claim promoted by the National Marfan Foundation at the urging of the New York State Health Department.


title: Jonathan Larson

text: "Rent" played on Broadway at the Nederlander Theatre from its debut in April 1996 until September 7, 2008. It is the 11th longest running show in Broadway history. In addition, it has toured throughout the United States, Canada, Brazil, Japan, United Kingdom, Australia, China, Singapore, Philippines, Mexico, Germany, Poland, and throughout Europe, as well as in other locations. A film version of "Rent" was released in 2005.


title: Jonathan Larson

text: After his death, Larson's family and friends started the Jonathan Larson Performing Arts Foundation to provide monetary grants to artists, especially musical theatre composers and writers, to support their creative work. The Jonathan Larson Grants are now administered by the American Theatre Wing, thanks to an endowment funded by the Foundation and the Larson Family.


title: Jonathan Larson

text: In December 2003, Larson's work was given to the Library of Congress. The collection includes numerous musicals, revues, cabarets, pop songs, dance and video projects – both produced and un-produced.


title: Jonathan Larson

text: Less than three years after "Rent" closed on Broadway, the show was revived Off-Broadway at Stage 1 of New World Stages just outside the Theater District. The show was directed by Michael Greif, who had directed the original productions. The show began previews on July 14, 2011, and opened August 11, 2011.


title: Jonathan Larson

text: From October 9 to 14, 2018, Feinstein's/54 Below presented "The Jonathan Larson Project", a concert of several previously unheard songs by Larson. The show was conceived and directed by Jennifer Ashley Tepper. It starred George Salazar, Lauren Marcus, Andy Mientus, Krysta Rodriguez, and Nick Blaemire. A CD of the show was released by Ghostlight Records in April 2019.


title: Jonathan Larson

text: Jonathan is portrayed by actor Andrew Garfield in the biographical musical drama "Tick, Tick... Boom!" which was released on the streaming service Netflix on November 19, 2021. The film received generally positive reviews from critics, with high praise for director Lin-Manuel Miranda’s direction in his directorial debut, score, and musical sequences, and Garfield's performance garnering universal acclaim. It was named one of the best films of 2021 by the American Film Institute, and was nominated for the Academy Award for Best Actor, Golden Globe Award for Best Motion Picture – Musical or Comedy and Golden Globe Award for Best Actor – Motion Picture Musical or Comedy (Garfield) at the 79th Golden Globe Awards, with Garfield winning the latter.


title: Jonathan Larson

text: In memory of Larson, in 1996, the Larson family along with the Jonathan Larson Performing Arts Foundation established an award honoring emerging musical theater writers and composers. In 2008, the American Theatre Wing adopted and continued on the legacy through the Jonathan Larson Grants, an unrestricted cash gift to aid in the creative endeavors of the writers and promote their work. Notable winners of the grant include Dave Malloy, Laurence O'Keefe, Nell Benjamin, Amanda Green, Joe Iconis, Pasek and Paul, Shaina Taub and Michael R. Jackson.


title: Jonathan Larson

text: In college, Larson dated Victoria Leacock. He also dated a dancer for four years who sometimes left him for other men, though she eventually left him for a woman. These experiences influenced the autobiographical aspects of "Rent".


title: Jonathan Larson

text: Larson lived and died in a loft with no heat on the fifth floor of 508 Greenwich Street, on the corner of Greenwich Street and Spring Street in Lower Manhattan. He lived with various roommates over the years, including Greg Beals, a journalist for "Newsweek" magazine and the brother of actress Jennifer Beals. For a while, he and his roommates kept an illegal wood-burning stove because of lack of heat in their building.


title: Jonathan Larson

text: From the spring of 1985, when he was 25 years old, until October 21, 1995, when he quit since "Rent" was being produced by the New York Theatre Workshop, Larson worked as a waiter at the Moondance Diner on the weekends and worked on composing and writing musicals during the week. Many people came to the diner to meet Larson. He was involved in writing the employee manual. At the diner, Larson met Jesse L. Martin, who was his waiting trainee and later performed the role of Tom Collins in the original cast of Larson's "Rent".


title: Harry Maguire

text: Jacob Harry Maguire (born 5 March 1993) is an English professional footballer who plays as a centre-back for club Manchester United and the England national team.


title: Harry Maguire

text: Maguire came through the youth system at Sheffield United before graduating to the first team in 2011. He totalled 166 professional games for the club and was their Player of the Year three consecutive times, also featuring in the PFA Team of the Year for League One as many times. In 2014, he transferred to Hull City for £2.5 million, who loaned him to Wigan Athletic in 2015. He joined Leicester City in 2017 for an initial fee of £12 million. Two years later, he moved to Manchester United for a fee believed to be £80 million, a world-record amount for a defender, and within six months was appointed the club captain.


title: Harry Maguire

text: Maguire played one match for England under-21 in 2012. In October 2017, he made his senior debut and he was chosen for the England's squads for the 2018 FIFA World Cup, 2022 FIFA World Cup and UEFA Euro 2020, earning a place in the Team of the Tournament in the latter.


title: Harry Maguire

text: Maguire was born in Sheffield, South Yorkshire, and was raised in the nearby village of Mosborough. His brothers, Joe and Laurence, are also footballers. He attended Immaculate Conception Catholic Primary School in Spinkhill and St Mary's Roman Catholic High School in Chesterfield. From 7 to 16 years old, Maguire played as central midfielder for Sheffield United's academy.


title: Harry Maguire

text: After coming through the youth system at Sheffield United, and with the team struggling against relegation, Maguire was promoted to the first-team squad, making his debut after coming on as a half-time substitute and winning the man of the match award in a home match against Cardiff City in April 2011. He made four further appearances that season but could not prevent the club from being relegated to League One.


title: Harry Maguire

text: Having cemented his place in the first team Maguire scored his first goal for the Blades in a 2–0 win at Oldham Athletic on the opening day of the 2011–12 League One season. Having been ever present from the start of the season Maguire was handed an extended deal in October to keep him at Bramall Lane until 2015. He continued in great form as the Blades pushed for promotion from League One and was rewarded at the end of the season when he was named as both "Player of the Year" and "Young Player of the Year" by the club. The BBC's Match of the Day magazine selected Maguire in its League One Team of The Year for 2011–12.


title: Harry Maguire

text: Maguire went into the following season as first choice in the centre of defence and his good form continued as he scored a brace in a Football League Trophy tie in a 4–1 victory over Notts County at Meadow Lane on 17 October 2012. By the end of February 2013 Maguire had made his 100th start for the Blades in a 0–0 draw against Leyton Orient at Bramall Lane at the age of just 19.


title: Harry Maguire

text: On 21 June 2014, it was revealed that United had offered Maguire an improved contract amid interest from Hull City and Wolverhampton Wanderers in signing Maguire with United already rejecting a £1 million and an improved £1.5 million bid from Wolves.


title: Harry Maguire

text: On 29 July 2014, Maguire joined Hull City in a deal worth £2.5 million, signing a three-year contract. He made his debut for the Tigers on 21 August in the UEFA Europa League play-off round first leg away to Lokeren of Belgium, a 1–0 defeat. He did not make his Premier League debut until 20 December, when he replaced the injured Curtis Davies for the final 13 minutes of a home loss by the same score against Swansea City.


title: Harry Maguire

text: After making only six appearances across all competitions at Hull, Maguire joined Wigan Athletic of the Championship on a one-month loan deal on 10 February 2015. A week later, he debuted in a 1–0 win at Reading. On 28 February, he scored a header from Jermaine Pennant's cross in a 3–1 win away to Blackpool. Having played as many games in his month-long loan as he had for Hull in the first half of the season, Maguire's stay at the DW Stadium was extended until the end of the season.


title: Harry Maguire

text: While Maguire was out on loan, Hull had been relegated to the Championship. On 28 May 2016, they won promotion back with a 1–0 play-off final win over Sheffield Wednesday at Wembley Stadium, with him replacing goalscorer Mohamed Diamé in the final minute.


title: Harry Maguire

text: In 2016–17, manager Mike Phelan made Maguire into a first-team regular. Maguire scored his first goal for Hull in a 2–1 EFL Cup win against Bristol City on 25 October 2016. Maguire captained Hull in their league victory against Middlesbrough on 5 April 2017 and scored his first Premier League goal in the 4–2 win. In a season that ended with relegation, he was voted Hull's Player of the Year by both the fans and the players.


title: Harry Maguire

text: On 15 June 2017, Maguire signed for Premier League club Leicester City on a five-year contract for an initial £12 million fee, potentially rising to £17 million with add-ons. He made his debut on 11 August as the season began with a 4–3 loss at Arsenal, and eight days later he scored his first goal for the Foxes, heading in Riyad Mahrez's corner to conclude a 2–0 win over Brighton & Hove Albion at the King Power Stadium. He played in every minute of the 2017–18 season and was awarded player of the season, as well as players' player of the season at the club's end of season awards.


title: Harry Maguire

text: Amid speculation about a transfer to Manchester United for a potential world-record fee for a defender, Maguire's Leicester manager Claude Puel confirmed on transfer deadline day of 9 August 2018 that Maguire would stay at the club, his only travel to Manchester being to face United with the Leicester squad in the fixture the evening after.


title: Harry Maguire

text: In July 2019, Manchester United made a £70 million bid for Maguire, a year after the club backed down from a deal because the same fee was considered too high. They made an improved bid, believed to be £80 million, which was accepted by Leicester on 2 August. The fee surpassed the £75 million Liverpool paid for Virgil van Dijk in January 2018, making Maguire the world's most expensive defender. The transfer was completed on 5 August, with Maguire signing a six-year contract with the option of a further year. He made his United debut in their opening match of the Premier League season, a 4–0 home victory over Chelsea on 11 August, and received the Man of the Match award.


title: Harry Maguire

text: On 17 January 2020, he was named as the new club captain by manager Ole Gunnar Solskjær following Ashley Young's departure to Inter Milan. Nine days later, he opened up a 6–0 FA Cup win against Tranmere Rovers by scoring his first goal for United. He scored his first Premier League goal for United on 17 February against Chelsea in a 2–0 away win. On 27 June, after the 3-month delay caused by the COVID-19 pandemic, United's FA Cup run resumed with a quarter-final tie against Norwich City which finished 2–1, Maguire scoring the winning goal deep into extra time. Maguire played a significant part in United's successful 2019–20 Premier League campaign, which saw them finish in third place, their second-highest league finish since the retirement of Sir Alex Ferguson. Maguire played in every minute of United's 38 game league campaign, becoming the first outfield player to do so for the club since 1995.


title: Harry Maguire

text: On 17 October 2020, Maguire scored his first goal of the season, equalising in the 23rd minute in a league match against Newcastle United that eventually ended in a 4–1 away win. On 27 January 2021, he equalised in the 64th minute even though the match ended in a 2–1 home loss against his former club Sheffield United, which ended a 13-match unbeaten run since the team lost to Arsenal on 1 November 2020. When several teammates received racist threats following the loss, Maguire joined other past and present United players condemning the abuse. He played the full 90 minutes on 2 February in United's Premier League record-equalling 9–0 home win against Southampton.


title: Harry Maguire

text: On 25 April, he equalled Gary Pallister's club record for playing the most number of league games without being substituted, by playing the full 90 minutes for the 71st consecutive Premier League game, in a scoreless draw against Leeds United. However, he couldn't break the record, as he had to be substituted in the 72nd minute of the subsequent game on 9 May, a 3–1 home win over Aston Villa, owing to an ankle injury. On 26 May, Maguire missed the 2021 UEFA Europa League Final against Villarreal due to injury, in which United lost on penalties after a 1–1 draw.


title: Harry Maguire

text: Maguire qualified to play for England, as well as Northern Ireland and the Republic of Ireland through his grandparents However, he was called up to the England national under-21 team for the first time in November 2012 for a friendly against Northern Ireland. Danny Wilson stated "He has got a fantastic maturity for his age, he takes everything in his stride and nothing fazes him. I don't expect this call-up to either because he is such a level headed character." Maguire duly made his England under-21 debut as a substitute in the 60th minute, coming on for Liverpool's Andre Wisdom in a 2–0 win against Northern Ireland Under-21s at Bloomfield Road.


title: Harry Maguire

text: On 24 August 2017, England manager Gareth Southgate included Maguire in his squad for the 2018 FIFA World Cup qualification matches against Malta and Slovakia. He made his debut when starting in England's 1–0 away win over Lithuania, which was the team's final match in their successful World Cup qualification campaign.


title: Harry Maguire

text: Maguire was named in the 23-man England squad for the 2018 FIFA World Cup. He assisted Harry Kane's winner against Tunisia on 18 June 2018 in England's World Cup opener. England won 2–1. Maguire scored his first England goal on 7 July with a 30th-minute header from Ashley Young's cross in a 2–0 win over Sweden in the quarter-finals.


title: Harry Maguire

text: At Euro 2020, he played his first match against Czech Republic in the last fixture of the group stage. Afterwards, he featured in the round of 16, when England won 2–0 against Germany, for which he was awarded the Star of the Match. On 3 July 2021, Maguire scored the second goal for England in a 4–0 win over Ukraine in the quarter-finals. Maguire started in the semi-finals against Denmark and in the final against Italy. England drew 1–1 after 120 minutes; in the resulting penalty shoot-out Maguire scored England's second penalty. However, England would lose 3–2. His performances during the tournament earned him a place in the UEFA Euro 2020 Team of the Tournament.


title: Harry Maguire

text: On 15 November 2021, Maguire scored the opening goal in a 10–0 victory over San Marino on the final day of 2022 FIFA World Cup qualification, making him England's highest scoring defender with seven goals, surpassing John Terry and Jack Charlton.


title: Harry Maguire

text: In February 2018, Maguire got engaged to his long-term girlfriend Fern Hawkins after seven years of dating. The couple married on 25 June 2022 at the Chateau de Varennes in South Burgundy, France. On 3 April 2019, Maguire revealed on his Instagram page that Hawkins had given birth to their first child, a daughter. Maguire and Hawkins had their second daughter on 9 May 2020.


title: Harry Maguire

text: On 21 August 2020, Maguire was arrested on the Greek island of Mykonos after an incident involving the police. Manchester United said in a statement that Maguire was "fully co-operating with the Greek authorities." Maguire appeared in court on the island of Syros the following day, after spending two days in detention. He was released from custody with his trial postponed until 25 August. On 25 August, Maguire was convicted of all charges, and found guilty of aggravated assault, resisting arrest and attempted bribery by a court on the island of Syros. Maguire was absent at the court ruling. The same day, Maguire was given a suspended jail term of 21 months and 10 days as it was a first offence and the three charges were classed as misdemeanours.


title: Harry Maguire

text: On 26 August 2020, Maguire's legal team lodged an appeal against the court verdict. While Manchester United and some British media sources have asserted that his conviction is nullified, this is disputed by the prosecution. On 5 March 2021, it was reported that Maguire's appeal was unlikely to take place in 2021, and that while the prosecution are keen for the case to be resolved as quickly as possible, proceedings could theoretically be delayed until 2028.


title: Harry Maguire

text: In 2022, Maguire was targeted with a bomb threat, resulting in the police sweeping his house for devices.


title: DNA

text: Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.


title: DNA

text: The two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases (cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds (known as the phospho-diester linkage) between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, pyrimidines and purines. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine.


title: DNA

text: Both strands of double-stranded DNA store the same biological information. This information is replicated when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences. The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (or "bases"). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription, where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes uracil (U). Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation.


title: DNA

text: Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms (animals, plants, fungi and protists) store most of their DNA inside the cell nucleus as nuclear DNA, and some in the mitochondria as mitochondrial DNA or in chloroplasts as chloroplast DNA. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm, in circular chromosomes. Within eukaryotic chromosomes, chromatin proteins, such as histones, compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.


title: DNA

text: DNA is a long polymer made from repeating units called nucleotides, each of which is usually symbolized by a single letter: either , , , or . The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, and have the same pitch of . The pair of chains have a radius of . According to another study, when measured in a different solution, the DNA chain measured wide, and one nucleotide unit measured long. Although each individual nucleotide is very small, a DNA polymer can be very long and may contain hundreds of millions of nucleotides, such as in chromosome 1. Chromosome 1 is the largest human chromosome with approximately 220 million base pairs, and would be long if straightened.


title: DNA

text: DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together. These two long strands coil around each other, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside, and a base linked to a sugar and to one or more phosphate groups is called a nucleotide. A biopolymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.


title: DNA

text: The backbone of the DNA strand is made from alternating phosphate and sugar groups. The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These are known as the 3′-end (three prime end), and 5′-end (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers directionality (sometimes called polarity) to each DNA strand. In a nucleic acid double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the related pentose sugar ribose in RNA.


title: DNA

text: The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. The four bases found in DNA are adenine (), cytosine (), guanine () and thymine (). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine, forming and base pairs.


title: DNA

text: The nucleobases are classified into two types: the purines, and , which are fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings and . A fifth pyrimidine nucleobase, uracil (), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.


title: DNA

text: Modified bases occur in DNA. The first of these recognized was 5-methylcytosine, which was found in the genome of "Mycobacterium tuberculosis" in 1925. The reason for the presence of these noncanonical bases in bacterial viruses (bacteriophages) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses. Modifications of the bases cytosine and adenine, the more common and modified DNA bases, play vital roles in the epigenetic control of gene expression in plants and animals.


title: DNA

text: A number of noncanonical bases are known to occur in DNA. Most of these are modifications of the canonical bases plus uracil.


title: DNA

text: Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. The major groove is wide, while the minor groove is in width. Due to the larger width of the major groove, the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell "(see below)", but the major and minor grooves are always named to reflect the differences in width that would be seen if the DNA was twisted back into the ordinary B form.


title: DNA

text: In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix (from six-carbon ring to six-carbon ring) is called a Watson-Crick base pair. DNA with high GC-content is more stable than DNA with low -content. A Hoogsteen base pair (hydrogen bonding the 6-carbon ring to the 5-carbon ring) is a rare variation of base-pairing. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature. As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms.


title: DNA

text: As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperatures, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).


title: DNA

text: The stability of the dsDNA form depends not only on the -content (% basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the melting temperature (also called "T" value), which is the temperature at which 50% of the double-strand molecules are converted to single-strand molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high -content have more strongly interacting strands, while short helices with high content have more weakly interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the Pribnow box in some promoters, tend to have a high content, making the strands easier to pull apart.


title: DNA

text: In the laboratory, the strength of this interaction can be measured by finding the melting temperature "T" necessary to break half of the hydrogen bonds. When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.


title: DNA

text: A DNA sequence is called a "sense" sequence if it is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.


title: DNA

text: A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.


title: DNA

text: DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.


title: DNA

text: DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, and the presence of polyamines in solution.


title: DNA

text: The first published reports of A-DNA X-ray diffraction patterns—and also B-DNA—used analyses based on Patterson functions that provided only a limited amount of structural information for oriented fibers of DNA. An alternative analysis was proposed by Wilkins "et al." in 1953 for the "in vivo" B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double helix.


title: DNA

text: Although the "B-DNA form" is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.


title: DNA

text: Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.


title: DNA

text: For many years, exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1 was announced, though the research was disputed, and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.


title: DNA

text: At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.


title: DNA

text: These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases, known as a guanine tetrad, form a flat plate. These flat four-base units then stack on top of each other to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.


title: DNA

text: In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.


title: DNA

text: In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible. Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.


title: DNA

text: Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named Hachimoji DNA. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence could be seen as an indication that there is nothing special about the four natural nucleobases that evolved on Earth. On the other hand, DNA is tightly related to RNA which does not only act as a transcript of DNA but also performs as moleular machines many tasks in cells. For this purpose it has to fold into a structure. It has been shown that to allow to create all possible structures at least four bases are required for the corresponding RNA, while a higher number is also possible but this would be against the natural principle of least effort.


title: DNA

text: The phosphate groups of DNA give it similar acidic properties to phosphoric acid and it can be considered as a strong acid. It will be fully ionized at a normal cellular pH, releasing protons which leave behind negative charges on the phosphate groups. These negative charges protect DNA from breakdown by hydrolysis by repelling nucleophiles which could hydrolyze it.


title: DNA

text: The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.


title: DNA

text: For one example, cytosine methylation produces 5-methylcytosine, which is important for X-inactivation of chromosomes. The average level of methylation varies between organisms—the worm "Caenorhabditis elegans" lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations. Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain, and the glycosylation of uracil to produce the "J-base" in kinetoplastids.


title: DNA

text: DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. A typical human cell contains about 150,000 bases that have suffered oxidative damage. Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations. These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer. DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.


title: DNA

text: Many mutagens fit into the space between two adjacent base pairs, this is called "intercalation". Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen. Others such as benzo["a"]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication. Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.


title: DNA

text: DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In an alternative fashion, a cell may copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.


title: DNA

text: Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which control transcription of the open reading frame.


title: DNA

text: In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences. The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or "C-value", among species, represent a long-standing puzzle known as the "C-value enigma". However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.


title: DNA

text: Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes. An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.


title: DNA

text: A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called "codons" formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).


title: DNA

text: In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (4 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAG, TAA, and TGA codons, (UAG, UAA, and UGA on the mRNA).


title: DNA

text: Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix. In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.


title: DNA

text: Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L. Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer; it may provide nutrients; and it may act as a buffer to recruit or titrate ions or antibiotics. Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm; it may contribute to biofilm formation; and it may contribute to the biofilm's physical strength and resistance to biological stress.


title: DNA

text: Cell-free fetal DNA is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus.


title: DNA

text: Under the name of environmental DNA eDNA has seen increased use in the natural sciences as a survey tool for ecology, monitoring the movements and presence of species in water, air, or on land, and assessing an area's biodiversity.


title: DNA

text: Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA, which allow neutrophils, a type of white blood cell, to kill extracellular pathogens while minimizing damage to the host cells.


title: DNA

text: All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.


title: DNA

text: Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation, and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.


title: DNA

text: A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.


title: DNA

text: In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.


title: DNA

text: As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes. Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.


title: DNA

text: Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5′-GATATC-3′ and makes a cut at the horizontal line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system. In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.


title: DNA

text: Enzymes called DNA ligases can rejoin cut or broken DNA strands. Ligases are particularly important in lagging strand DNA replication, as they join the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.


title: DNA

text: Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break. Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix. Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.


title: DNA

text: Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands. These enzymes are essential for most processes where enzymes need to access the DNA bases.


title: DNA

text: Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products is created based on existing polynucleotide chains—which are called "templates". These enzymes function by repeatedly adding a nucleotide to the 3′ hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5′ to 3′ direction. In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.


title: DNA

text: In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ exonuclease activity is activated and the incorrect base removed. In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.


title: DNA

text: RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres. For example, HIV reverse transcriptase is an enzyme for AIDS virus replication. Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. It synthesizes telomeres at the ends of chromosomes. Telomeres prevent fusion of the ends of neighboring chromosomes and protect chromosome ends from damage.


title: DNA

text: Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.


title: DNA

text: A DNA helix usually does not interact with other segments of DNA, and in human cells, the different chromosomes even occupy separate areas in the nucleus called "chromosome territories". This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.


title: DNA

text: Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins. Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.


title: DNA

text: The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51. The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA. A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA. Only strands of like polarity exchange DNA during recombination. There are two types of cleavage: east-west cleavage and north–south cleavage. The north–south cleavage nicks both strands of DNA, while the east–west cleavage has one strand of DNA intact. The formation of a Holliday junction during recombination makes it possible for genetic diversity, genes to exchange on chromosomes, and expression of wild-type viral genomes.