This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and 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 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.
MRE11 has a role in 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 cancer syndromes). (Also see 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.
^Lukaszewicz A, Howard-Till RA, Novatchkova M, Mochizuki K, Loidl J (October 2010). "MRE11 and COM1/SAE2 are required for double-strand break repair and efficient chromosome pairing during meiosis of the protist Tetrahymena". Chromosoma. 119 (5): 505–18. doi:10.1007/s00412-010-0274-9. PMID20422424.
^Yuan SS, Hou MF, Hsieh YC, Huang CY, Lee YC, Chen YJ, Lo S (2012). "Role of MRE11 in cell proliferation, tumor invasion, and DNA repair in breast cancer". J. Natl. Cancer Inst. 104 (19): 1485–502. doi:10.1093/jnci/djs355. PMID22914783.
^ abChiba N, Parvin JD (2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem. 276 (42): 38549–54. doi:10.1074/jbc.M105227200. PMID11504724.
^Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH (1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science. 285 (5428): 747–50. doi:10.1126/science.285.5428.747. PMID10426999.
^ abGoedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nat. Genet. 23 (2): 194–8. doi:10.1038/13821. PMID10508516.
^Xu X, Stern DF (2003). "NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors". FASEB J. 17 (13): 1842–8. doi:10.1096/fj.03-0310com. PMID14519663.
^ abTrujillo KM, Yuan SS, Lee EY, Sung P (1998). "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95". J. Biol. Chem. 273 (34): 21447–50. doi:10.1074/jbc.273.34.21447. PMID9705271.
^Cerosaletti KM, Concannon P (2003). "Nibrin forkhead-associated domain and breast cancer C-terminal domain are both required for nuclear focus formation and phosphorylation". J. Biol. Chem. 278 (24): 21944–51. doi:10.1074/jbc.M211689200. PMID12679336.
^Zhu XD, Küster B, Mann M, Petrini JH, de Lange T (2000). "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres". Nat. Genet. 25 (3): 347–52. doi:10.1038/77139. PMID10888888.
Carney JP, Maser RS, Olivares H, et al. (1998). "The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.". Cell. 93 (3): 477–86. doi:10.1016/S0092-8674(00)81175-7. PMID9590181.
Trujillo KM, Yuan SS, Lee EY, Sung P (1998). "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95.". J. Biol. Chem. 273 (34): 21447–50. doi:10.1074/jbc.273.34.21447. PMID9705271.
Chamankhah M, Wei YF, Xiao W (1999). "Isolation of hMRE11B: failure to complement yeast mre11 defects due to species-specific protein interactions.". Gene. 225 (1-2): 107–16. doi:10.1016/S0378-1119(98)00530-7. PMID9931460.
Goedecke W, Eijpe M, Offenberg HH, et al. (1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis.". Nat. Genet. 23 (2): 194–8. doi:10.1038/13821. PMID10508516.
Kim ST, Lim DS, Canman CE, Kastan MB (2000). "Substrate specificities and identification of putative substrates of ATM kinase family members.". J. Biol. Chem. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID10608806.
Stewart GS, Maser RS, Stankovic T, et al. (2000). "The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder.". Cell. 99 (6): 577–87. doi:10.1016/S0092-8674(00)81547-0. PMID10612394.
Hopfner KP, Karcher A, Craig L, et al. (2001). "Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase.". Cell. 105 (4): 473–85. doi:10.1016/S0092-8674(01)00335-X. PMID11371344.
Pitts SA, Kullar HS, Stankovic T, et al. (2001). "hMRE11: genomic structure and a null mutation identified in a transcript protected from nonsense-mediated mRNA decay.". Hum. Mol. Genet. 10 (11): 1155–62. doi:10.1093/hmg/10.11.1155. PMID11371508.
Chiba N, Parvin JD (2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage.". J. Biol. Chem. 276 (42): 38549–54. doi:10.1074/jbc.M105227200. PMID11504724.