DNA's Wizardly Way of Healing Itself

A chemical group attached to one end of a DNA molecule appears to cause a patch of damaged DNA far down the double helix to be mended. This startling case of "chemistry at a distance," as one scientist calls it, suggests that long-range DNA repair of some kind might play a role in normal cells. The finding, reported in today's issue of Science,* might also point the way to therapies that could patch up damaged DNA, forestalling cancer.

A team of chemists at the California Institute of Technology led by Jackie Barton fabricated DNA helices with built-in damage: a small kink in the helix called a thymine dimer. This is the kind of damage caused by the sun's ultraviolet rays, and it can be a first step toward the deadly skin cancer melanoma. Next, they inserted an electron-accepting metal complex at the end of the DNA. Exposing the sample to light excites the metal compound, triggering it to absorb an electron from the thymine dimer and repair the DNA damage. Because the compound can catalyze the repair reaction over and over, Barton says that the experiment "may represent a strategy to rationally design molecules that can accomplish this kind of repair therapeutically." In DNA's core, base pairs form a so-called BORDER=0> stack (gray, shown in top and side views) along which electrons may tunnel from a distant site to an artificial electron acceptor (yellow).

And because the electron released by the thymine dimer has to travel down the DNA helix to the metal compound, the result may suggest that DNA's unique structure allows it to behave like a conductive wire--unlike proteins, which are insulating. Barton thinks electrons can "tunnel" through the channel that runs down the center of the joined bases of the helix. "There is no question that these results are saying DNA is a different system than proteins," she says.

The chemistry-at-a-distance feat has impressed other researchers, but they are divided about what it says about DNA's electrical properties. Barton's experiments "show unambiguously that there's long-range chemistry that can be performed on DNA, and that electron transfer can be accomplished," says Columbia University's Nick Turro. Others, however, think the chemical change can be explained in a more conventional picture, in which the electrons hop from atom to atom on the DNA rather than tunneling down the helix in one step. That would be chemistry at a distance, says University of North Carolina chemist Holden Thorp, "with a believable mechanism. And there's a lot of cool stuff [Barton] could do with that."


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