MRE11A

Double-strand break repair protein MRE11A is a is_associated_with::protein that in humans is encoded by the MRE11A is_associated_with::gene.

Function
This gene encodes a nuclear protein involved in is_associated_with::homologous recombination, is_associated_with::telomere length maintenance, and DNA is_associated_with::double-strand break repair. By itself, the protein has 3' to 5' is_associated_with::exonuclease activity and is_associated_with::endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA is_associated_with::ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms.

Orthologs of MRE11A
Mre11, an ortholog of human MRE11A, occurs in the is_associated_with::prokaryote is_associated_with::archaeon Sulfolobus acidocaldarius. In this organism the Mre11 protein interacts with the is_associated_with::Rad50 protein and appears to have an active role in the repair of DNA damages experimentally introduced by gamma radiation. Similarly, during meiosis in the is_associated_with::eukaryotic protist is_associated_with::Tetrahymena Mre11 is required for repair of DNA damages, in this case is_associated_with::double-strand breaks, by a process that likely involves is_associated_with::homologous recombination. These observations suggest that human MRE11A is descended from prokaryotic and protist ancestral Mre11 proteins that served a role in early processes for repairing DNA damage.

MRE11 overexpression in cancer
MRE11 has a role in is_associated_with::microhomology-mediated end joining (MMEJ) repair of double strand breaks. It is one of 6 enzymes required for this error prone DNA repair pathway. MRE11 is over-expressed in breast cancers.

Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is less usual in cancer. For instance, at least 36 DNA repair enzymes, when mutationally defective in germ line cells, cause increased risk of cancer (hereditary is_associated_with::cancer syndromes). (Also see is_associated_with::DNA repair-deficiency disorder.) Similarly, at least 12 DNA repair genes have frequently been found to be epigenetically repressed in one or more cancers. (See also Epigenetically reduced DNA repair and cancer.) Ordinarily, deficient expression of a DNA repair enzyme results in increased un-repaired DNA damages which, through replication errors (translesion synthesis), lead to mutations and cancer. However, MRE11 mediated MMEJ repair is highly inaccurate, so in this case, over-expression, rather than under-expression, apparently leads to cancer.

Interactions
MRE11A has been shown to interact with:
 * ATM,
 * is_associated_with::BRCA1,
 * is_associated_with::Ku70,
 * is_associated_with::MDC1,
 * NBN,
 * is_associated_with::Rad50,   and
 * is_associated_with::TERF2.