The MRE11 Complex and DNA Damage Response

Thu, 01/23/2014 - 11:19

The maintenance of genome stability depends on the DNA damage response (DDR) which is a complex signaling network including cell cycle checkpoints, DNA repair and damage tolerance pathways. The DDR complex has the ability to sense DNA damage and transduce this information to the cell to influence cellular response to it. Failure of the DDR or associated events causes genomic instability, an underlining cause of several human syndromes and also associated with various age-related diseases, particularly cancer. The DDR pathway is initiated upon recognition of the DNA lesion by sensor proteins, followed by rapid and, in many cases, reversible changes in cell behavior. The DDR can also trigger specialized programs, such as apoptosis and senescence, to remove or minimize the risk posed by cells with genetic instability. [1]

The MRE11 complex which consists of MRE11, RAD50 and NBS1, a homologue of Xrs2 in Saccharomyces cerevisae, was first identified via screens for yeast genes involved in meiotic recombination, and resistance to DNA damage induced by UV light and X-rays. MRE11 has been viewed as the core of the complex, whereas the interaction between NBS1 and RAD50 is indirect and mediated through MRE11. Mre11 is a highly conserved 70–90 kDa protein composed of an N-terminal Mn2+/Mg2+-dependent phosphoesterase domain, and two distinct C-terminal DNA-binding domains. Isolated Mre11 forms stable dimers that possess a number biochemical activities including: (i) intrinsic DNA binding activity with the specific ability to synapse DSB termini, and (ii) endo- and exonuclease activities against a variety of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) substrates. While these nuclease activities contribute to both non-homologous end joining and homologous recombination, it should be noted that Mre11 conspicuously lacks the 5′→3′ exonuclease activity requisite for generating the long 3′ ssDNA overhangs necessary for HR. Although it is possible that a protein-binding partner might switch the polarity of the exonuclease activity of Mre11, it is more likely that Mre11 facilitates the activity of additional DSB processing factors. In both yeast and mammals a number of 5′→3′ exonucleases have been identified and are capable of contributing to the generation of 3′ overhangs during HR, giving weight to the idea that other enzymes act in concert with MRN complex. [2,3,4]

Immunohistochemistry: Mre11 Antibody Immunohistochemistry: Mre11 Antibody

The Rad50 and Mre11 proteins of the MRN complex are highly conserved, and homologs exist in archaeal, fission, and budding yeasts, as well as in higher metazoans. So far various mutations have been reported for MRN complex including Mre11 gene, for instance inherited mutations in Mre11 (located 11q21) cause ataxia-telangiectasia-like disease (ATLD) which is a rare variant of Ataxia telangiectasia. Mutations in this gene and aberrant expression contribute to tumorigenesis and cancer as well. [1]

Novus offers an extensive selection of MRE11 complex related reagents including:

  1. PMID:  21252998
  2. PMID:  20655309
  3. PMID:  17713585
  4. PMID:  19744924


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