MRE11A

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MRE11A
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MRE11A, ATLD, HNGS1, MRE11, MRE11B, MRE11 homolog A, double strand break repair nuclease
External IDs MGI: 1100512 HomoloGene: 4083 GeneCards: 4361
RNA expression pattern
PBB GE MRE11A 205395 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005590
NM_005591

NM_018736
NM_001310728

RefSeq (protein)

NP_005581.2
NP_005582.1

NP_001297657.1
NP_061206.1

Location (UCSC) Chr 11: 94.42 – 94.49 Mb Chr 9: 14.78 – 14.84 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Double-strand break repair protein MRE11A is a protein that in humans is encoded by the MRE11A gene.[3]

Function[edit]

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.[4]

Orthologs of MRE11A[edit]

Mre11, an ortholog of human MRE11A, occurs in the prokaryote archaeon Sulfolobus acidocaldarius.[5] In this organism the Mre11 protein interacts with the Rad50 protein and appears to have an active role in the repair of DNA damages experimentally introduced by gamma radiation.[5] Similarly, during meiosis in the eukaryotic protist Tetrahymena Mre11 is required for repair of DNA damages, in this case double-strand breaks,[6] by a process that likely involves 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[edit]

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.[7] MRE11 is over-expressed in breast cancers.[8]

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).[9] (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.[9] (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[edit]

MRE11A has been shown to interact with:

See also[edit]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Petrini JH, Walsh ME, DiMare C, Chen XN, Korenberg JR, Weaver DT (February 1996). "Isolation and characterization of the human MRE11 homologue". Genomics. 29 (1): 80–6. doi:10.1006/geno.1995.1217. PMID 8530104. 
  4. ^ "Entrez Gene: MRE11A MRE11 meiotic recombination 11 homolog A (S. cerevisiae)". 
  5. ^ a b Quaiser A, Constantinesco F, White MF, Forterre P, Elie C (2008). "The Mre11 protein interacts with both Rad50 and the HerA bipolar helicase and is recruited to DNA following gamma irradiation in the archaeon Sulfolobus acidocaldarius". BMC Mol. Biol. 9: 25. doi:10.1186/1471-2199-9-25. PMC 2288612free to read. PMID 18294364. 
  6. ^ 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. PMID 20422424. 
  7. ^ Sharma S, Javadekar SM, Pandey M, Srivastava M, Kumari R, Raghavan SC (2015). "Homology and enzymatic requirements of microhomology-dependent alternative end joining". Cell Death Dis. 6: e1697. doi:10.1038/cddis.2015.58. PMC 4385936free to read. PMID 25789972. 
  8. ^ 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. PMID 22914783. 
  9. ^ a b Bernstein C, Prasad AR, Nfonsam V, Bernstein H. (2013). DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-51-1114-6, InTech, http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer
  10. ^ Kim ST, Lim DS, Canman CE, Kastan MB (1999). "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. PMID 10608806. 
  11. ^ a b c d Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. doi:10.1101/gad.14.8.927. PMC 316544free to read. PMID 10783165. 
  12. ^ a b 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. PMID 11504724. 
  13. ^ Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (2001). "Direct DNA binding by Brca1". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6086–91. doi:10.1073/pnas.111125998. PMC 33426free to read. PMID 11353843. 
  14. ^ 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. PMID 10426999. 
  15. ^ a b Goedecke 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. PMID 10508516. 
  16. ^ 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. PMID 14519663. 
  17. ^ a b 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. PMID 9705271. 
  18. ^ 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. PMID 12679336. 
  19. ^ Matsuzaki K, Shinohara A, Shinohara M (2008). "Forkhead-associated domain of yeast Xrs2, a homolog of human Nbs1, promotes nonhomologous end joining through interaction with a ligase IV partner protein, Lif1". Genetics. 179 (1): 213–25. doi:10.1534/genetics.107.079236. PMC 2390601free to read. PMID 18458108. 
  20. ^ Desai-Mehta A, Cerosaletti KM, Concannon P (2001). "Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization". Mol. Cell. Biol. 21 (6): 2184–91. doi:10.1128/MCB.21.6.2184-2191.2001. PMC 86852free to read. PMID 11238951. 
  21. ^ Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JH (1996). "Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair". Mol. Cell. Biol. 16 (9): 4832–41. PMC 231485free to read. PMID 8756642. 
  22. ^ 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. PMID 10888888. 

Further reading[edit]