MRE11A

MRE11 meiotic recombination 11 homolog A (S. cerevisiae)
Identifiers
Symbols	MRE11A; ATLD; HNGS1; MRE11; MRE11B
External IDs	OMIM: 600814 MGI: 1100512 HomoloGene: 4083 GeneCards: MRE11A Gene
Gene Ontology Molecular function • single-stranded DNA specific endodeoxyribonuclease activity • DNA binding • double-stranded DNA binding • ATP-dependent DNA helicase activity • nuclease activity • endodeoxyribonuclease activity • protein binding • protein C-terminus binding • 3'-5' exonuclease activity • hydrolase activity • manganese ion binding Cellular component • chromosome, telomeric region • nuclear chromatin • condensed nuclear chromosome • nucleus • nucleoplasm • nucleolus • Mre11 complex • Mre11 complex • perinuclear region of cytoplasm Biological process • regulation of mitotic recombination • double-strand break repair via homologous recombination • DNA repair • double-strand break repair • double-strand break repair via nonhomologous end joining • DNA recombination • telomere maintenance via telomerase • sister chromatid cohesion • meiosis • reciprocal meiotic recombination • heart development • positive regulation of protein autophosphorylation • DNA duplex unwinding • negative regulation of DNA endoreduplication • positive regulation of kinase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4361	17535
Ensembl	ENSG00000020922	ENSMUSG00000031928
UniProt	P49959	Q3TU24
RefSeq (mRNA)	NM_005590.3	NM_018736.2
RefSeq (protein)	NP_005581.2	NP_061206.1
Location (UCSC)	Chr 11: 94.15 – 94.23 Mb	Chr 9: 14.59 – 14.64 Mb
PubMed search	[1]	[2]

Double-strand break repair protein MRE11A is a protein that in humans is encoded by the MRE11A gene.^[1]

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.^[2]

Interactions

MRE11A has been shown to interact with Ku70,^[3] Ataxia telangiectasia mutated,^[4][5] MDC1,^[6] Rad50,^{[3][5][7][8][9]} Nibrin,^{[5][9][10][11][12]} TERF2^[13] and BRCA1.^{[5][7][14][15]}

References

1. ^ Petrini JH, Walsh ME, DiMare C, Chen XN, Korenberg JR, Weaver DT (Feb 1996). "Isolation and characterization of the human MRE11 homologue". Genomics 29 (1): 80–6. doi:10.1006/geno.1995.1217. PMID 8530104. 
2. ^ "Entrez Gene: MRE11A MRE11 meiotic recombination 11 homolog A (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4361. 
3. ^ ^{a b} Goedecke, W; Eijpe M, Offenberg H H, van Aalderen M, Heyting C (Oct. 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nat. Genet. (UNITED STATES) 23 (2): 194–8. doi:10.1038/13821. ISSN 1061-4036. PMID 10508516. 
4. ^ Kim, S T; Lim D S, Canman C E, Kastan M B (Dec. 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. (UNITED STATES) 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. ISSN 0021-9258. PMID 10608806. 
5. ^ ^{a b c d} Wang, Y; Cortez D, Yazdi P, Neff N, Elledge S J, Qin J (Apr. 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. (UNITED STATES) 14 (8): 927–39. ISSN 0890-9369. PMC 316544. PMID 10783165. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316544. 
6. ^ Xu, Xingzhi; Stern David F (Oct. 2003). "NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors". FASEB J. (United States) 17 (13): 1842–8. doi:10.1096/fj.03-0310com. PMID 14519663. 
7. ^ ^{a b} Chiba, N; Parvin J D (Oct. 2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem. (United States) 276 (42): 38549–54. doi:10.1074/jbc.M105227200. ISSN 0021-9258. PMID 11504724. 
8. ^ Dolganov, G M; Maser R S, Novikov A, Tosto L, Chong S, Bressan D A, Petrini J H (Sep. 1996). "Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair". Mol. Cell. Biol. (UNITED STATES) 16 (9): 4832–41. ISSN 0270-7306. PMC 231485. PMID 8756642. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231485. 
9. ^ ^{a b} Trujillo, K M; Yuan S S, Lee E Y, Sung P (Aug. 1998). "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95". J. Biol. Chem. (UNITED STATES) 273 (34): 21447–50. doi:10.1074/jbc.273.34.21447. ISSN 0021-9258. PMID 9705271. 
10. ^ Cerosaletti, Karen M; Concannon Patrick (Jun. 2003). "Nibrin forkhead-associated domain and breast cancer C-terminal domain are both required for nuclear focus formation and phosphorylation". J. Biol. Chem. (United States) 278 (24): 21944–51. doi:10.1074/jbc.M211689200. ISSN 0021-9258. PMID 12679336. 
11. ^ Matsuzaki, Kenichiro; Shinohara Akira, Shinohara Miki (May. 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 (United States) 179 (1): 213–25. doi:10.1534/genetics.107.079236. ISSN 0016-6731. PMC 2390601. PMID 18458108. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2390601. 
12. ^ Desai-Mehta, A; Cerosaletti K M, Concannon P (Mar. 2001). "Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization". Mol. Cell. Biol. (United States) 21 (6): 2184–91. doi:10.1128/MCB.21.6.2184-2191.2001. ISSN 0270-7306. PMC 86852. PMID 11238951. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86852. 
13. ^ Zhu, X D; Küster B, Mann M, Petrini J H, de Lange T (Jul. 2000). "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres". Nat. Genet. (UNITED STATES) 25 (3): 347–52. doi:10.1038/77139. ISSN 1061-4036. PMID 10888888. 
14. ^ Paull, T T; Cortez D, Bowers B, Elledge S J, Gellert M (May. 2001). "Direct DNA binding by Brca1". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (11): 6086–91. doi:10.1073/pnas.111125998. ISSN 0027-8424. PMC 33426. PMID 11353843. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=33426. 
15. ^ Zhong, Q; Chen C F, Li S, Chen Y, Wang C C, Xiao J, Chen P L, Sharp Z D, Lee W H (Jul. 1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science (UNITED STATES) 285 (5428): 747–50. doi:10.1126/science.285.5428.747. ISSN 0036-8075. PMID 10426999. 

Further reading

• Dolganov GM, Maser RS, Novikov A, et al. (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 231485. PMID 8756642. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231485. 
• 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. PMID 9590181. 
• Paull TT, Gellert M (1998). "The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks.". Mol. Cell 1 (7): 969–79. doi:10.1016/S1097-2765(00)80097-0. PMID 9651580. 
• 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. 
• 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. PMID 9931460. 
• Zhong Q, Chen CF, Li S, et al. (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. 
• 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. PMID 10508516. 
• 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. PMID 10608806. 
• 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. PMID 10612394. 
• Wang Y, Cortez D, Yazdi P, et al. (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. PMC 316544. PMID 10783165. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316544. 
• Gatei M, Young D, Cerosaletti KM, et al. (2000). "ATM-dependent phosphorylation of nibrin in response to radiation exposure.". Nat. Genet. 25 (1): 115–9. doi:10.1038/75508. PMID 10802669. 
• Zhu XD, Küster B, Mann M, et al. (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. 
• de Vries H, Rüegsegger U, Hübner W, et al. (2000). "Human pre-mRNA cleavage factor II(m) contains homologs of yeast proteins and bridges two other cleavage factors.". EMBO J. 19 (21): 5895–904. doi:10.1093/emboj/19.21.5895. PMC 305781. PMID 11060040. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=305781. 
• Fukuda T, Sumiyoshi T, Takahashi M, et al. (2001). "Alterations of the double-strand break repair gene MRE11 in cancer.". Cancer Res. 61 (1): 23–6. PMID 11196167. 
• 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 86852. PMID 11238951. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86852. 
• Paull TT, Cortez D, Bowers B, et al. (2001). "Direct DNA binding by Brca1.". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6086–91. doi:10.1073/pnas.111125998. PMC 33426. PMID 11353843. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=33426. 
• 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. PMID 11371344. 
• 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. PMID 11371508. 
• 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.