Mre11

Summary

Gene Symbol: Mre11
Description: MRE11 homolog, double strand break repair nuclease
Alias: ATLD, HNGS1, MRE11A, MRE11B, double-strand break repair protein MRE11, AT-like disease, DNA recombination and repair protein, MRE11 double strand break repair nuclease A, MRE11 homolog 1, MRE11 homolog A, double strand break repair nuclease, MRE11 homolog, double strand break repair nuclease A, MRE11 meiotic recombination 11 homolog A, MRE11 meiotic recombination 11-like protein A, double-strand break repair protein MRE11A, endo/exonuclease Mre11, meiotic recombination 11 homolog 1, meiotic recombination 11 homolog A
Species: human
Products:     Mre11

Top Publications

  1. Zhuang J, Jiang G, Willers H, Xia F. Exonuclease function of human Mre11 promotes deletional nonhomologous end joining. J Biol Chem. 2009;284:30565-73 pubmed publisher
    ..Little is known about how these NHEJ subpathways are regulated. Mre11 has been implicated in DNA damage response, thus we investigated whether Mre11 function also extended to NHEJ...
  2. Schuetz J, MacArthur A, Leach S, Lai A, Gallagher R, Connors J, et al. Genetic variation in the NBS1, MRE11, RAD50 and BLM genes and susceptibility to non-Hodgkin lymphoma. BMC Med Genet. 2009;10:117 pubmed publisher
    ..The members of the MRE11-RAD50-NBS1 (MRN) complex and BLM have central roles in maintenance of DNA integrity...
  3. Goldberg M, Stucki M, Falck J, D Amours D, Rahman D, Pappin D, et al. MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature. 2003;421:952-6 pubmed
    b>MRE11, RAD50 and NBS1 form a highly conserved protein complex (the MRE11 complex) that is involved in the detection, signalling and repair of DNA damage...
  4. Wen Q, Scorah J, Phear G, Rodgers G, Rodgers S, Meuth M. A mutant allele of MRE11 found in mismatch repair-deficient tumor cells suppresses the cellular response to DNA replication fork stress in a dominant negative manner. Mol Biol Cell. 2008;19:1693-705 pubmed publisher
    The interaction of ataxia-telangiectasia mutated (ATM) and the Mre11/Rad50/Nbs1 (MRN) complex is critical for the response of cells to DNA double-strand breaks; however, little is known of the role of these proteins in response to DNA ..
  5. Paull T, Gellert M. The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol Cell. 1998;1:969-79 pubmed
    b>MRE11 and RAD50 are known to be required for nonhomologous joining of DNA ends in vivo...
  6. Ottini L, Falchetti M, Saieva C, De Marco M, Masala G, Zanna I, et al. MRE11 expression is impaired in gastric cancer with microsatellite instability. Carcinogenesis. 2004;25:2337-43 pubmed
    ..of MSI-H GCs, we analysed the poly(T)11 tract constituting an accessory splicing signal within the intron 4 of the MRE11 gene...
  7. Lukas C, Melander F, Stucki M, Falck J, Bekker Jensen S, Goldberg M, et al. Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J. 2004;23:2674-83 pubmed
    Mdc1/NFBD1 controls cellular responses to DNA damage, in part via interacting with the Mre11-Rad50-Nbs1 complex that is involved in the recognition, signalling, and repair of DNA double-strand breaks (DSBs)...
  8. Fernet M, Gribaa M, Salih M, Seidahmed M, Hall J, Koenig M. Identification and functional consequences of a novel MRE11 mutation affecting 10 Saudi Arabian patients with the ataxia telangiectasia-like disorder. Hum Mol Genet. 2005;14:307-18 pubmed
    ..All patients are homozygous for a novel missense mutation (630G-->C, W210C) of the MRE11 gene...
  9. Moreno Herrero F, de Jager M, Dekker N, Kanaar R, Wyman C, Dekker C. Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA. Nature. 2005;437:440-3 pubmed
    The human Rad50/Mre11/Nbs1 complex (hR/M/N) functions as an essential guardian of genome integrity by directing the proper processing of DNA ends, including DNA breaks...

More Information

Publications63

  1. Jazayeri A, Falck J, Lukas C, Bartek J, Smith G, Lukas J, et al. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol. 2006;8:37-45 pubmed
    ..Here, we show that ATM and the nuclease activity of meiotic recombination 11 (Mre11) are required for the processing of DNA double-strand breaks (DSBs) to generate the replication protein A (RPA)-..
  2. Jazayeri A, Balestrini A, Garner E, Haber J, Costanzo V. Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity. EMBO J. 2008;27:1953-62 pubmed publisher
    DNA double-strand breaks (DSBs) can be processed by the Mre11-Rad50-Nbs1 (MRN) complex, which is essential to promote ataxia telangiectasia-mutated (ATM) activation...
  3. Choudhury A, Elliott F, Iles M, Churchman M, Bristow R, Bishop D, et al. Analysis of variants in DNA damage signalling genes in bladder cancer. BMC Med Genet. 2008;9:69 pubmed publisher
    ..DNA was extracted from a peripheral blood sample and genotyping of 24 SNPs in MRE11, NBS1, RAD50, H2AX and ATM was undertaken using an allelic discrimination method (Taqman)...
  4. Bartkova J, Tommiska J, Oplustilova L, Aaltonen K, Tamminen A, Heikkinen T, et al. Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer: MRE11 as a candidate familial cancer-predisposing gene. Mol Oncol. 2008;2:296-316 pubmed publisher
    The MRE11, RAD50, and NBS1 genes encode proteins of the MRE11-RAD50-NBS1 (MRN) complex critical for proper maintenance of genomic integrity and tumour suppression; however, the extent and impact of their cancer-predisposing defects, and ..
  5. Stewart G, Maser R, Stankovic T, Bressan D, Kaplan M, Jaspers N, et al. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell. 1999;99:577-87 pubmed
    ..in hMRE11, but not in ATM, are present in certain individuals with an ataxia-telangiectasia-like disorder (ATLD)...
  6. Schlacher K, Christ N, Siaud N, Egashira A, Wu H, Jasin M. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell. 2011;145:529-42 pubmed publisher
    ..BRCA2 prevents chromosomal aberrations on replication stalling, which are alleviated by inhibition of MRE11, the nuclease responsible for this form of fork instability...
  7. Hsu H, Wang H, Chen S, Hsu G, Shen C, Yu J. Breast cancer risk is associated with the genes encoding the DNA double-strand break repair Mre11/Rad50/Nbs1 complex. Cancer Epidemiol Biomarkers Prev. 2007;16:2024-32 pubmed
    The evolutionarily conserved Mre11-Rad50-Nbs1 (MRN) complex, consisting of proteins encoded by the genes Mre11, Rad50, and Nbs1, was recently shown to play a crucial role in DNA double-strand break (DSB) repair by recruiting the nuclear ..
  8. Bhaskara V, Dupré A, Lengsfeld B, Hopkins B, Chan A, Lee J, et al. Rad50 adenylate kinase activity regulates DNA tethering by Mre11/Rad50 complexes. Mol Cell. 2007;25:647-61 pubmed
    b>Mre11 and Rad50 are the catalytic components of a highly conserved DNA repair complex that functions in many aspects of DNA metabolism involving double-strand breaks...
  9. Stucki M, Clapperton J, Mohammad D, Yaffe M, Smerdon S, Jackson S. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell. 2005;123:1213-26 pubmed
    ..Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian response to DNA damage. ..
  10. Choudhury A, Nelson L, Teo M, Chilka S, Bhattarai S, Johnston C, et al. MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res. 2010;70:7017-26 pubmed publisher
    ..Protein expression of MRE11, RAD50, NBS1, ATM, and H2AX was studied by immunohistochemistry in pretreatment tumor specimens from two cohorts ..
  11. Chen L, Morio T, Minegishi Y, Nakada S, Nagasawa M, Komatsu K, et al. Ataxia-telangiectasia-mutated dependent phosphorylation of Artemis in response to DNA damage. Cancer Sci. 2005;96:134-41 pubmed
    ..In support of this functional link, hyperphosphorylated Artemis was found to physically associate with the Mre11/Rad50/Nbs1 complex in an ATM-dependent manner in response to IR-induced DNA double strand breaks (DSB)...
  12. Robison J, Lu L, Dixon K, Bissler J. DNA lesion-specific co-localization of the Mre11/Rad50/Nbs1 (MRN) complex and replication protein A (RPA) to repair foci. J Biol Chem. 2005;280:12927-34 pubmed
    ..stress or DNA damage, involves the activation of DNA repair and cell cycle regulatory proteins including the MRN (Mre11, Rad50, and Nbs1) complex and replication protein A (RPA)...
  13. Takemura H, Rao V, Sordet O, Furuta T, Miao Z, Meng L, et al. Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in colorectal carcinoma cells in response to replication-dependent DNA double strand breaks. J Biol Chem. 2006;281:30814-23 pubmed
    The Mre11.Rad50.Nbs1 (MRN) complex binds DNA double strand breaks to repair DNA and activate checkpoints. We report MRN deficiency in three of seven colon carcinoma cell lines of the NCI Anticancer Drug Screen...
  14. Giannini G, Rinaldi C, Ristori E, Ambrosini M, Cerignoli F, Viel A, et al. Mutations of an intronic repeat induce impaired MRE11 expression in primary human cancer with microsatellite instability. Oncogene. 2004;23:2640-7 pubmed
    ..have shown that shortening of the poly(T)11 within the polypyrimidine stretch/accessory splicing signal of human MRE11 leads to the reduced expression and functional impairment of the MRE11/NBS1/RAD50 complex...
  15. Gao J, Zhang H, Arbman G, Sun X. RAD50/MRE11/NBS1 proteins in relation to tumour development and prognosis in patients with microsatellite stable colorectal cancer. Histol Histopathol. 2008;23:1495-502 pubmed publisher
    RAD50/MRE11/NBS1 complex is essential for DNA double-strand break repair and for maintaining genomic integrity...
  16. Herbig U, Jobling W, Chen B, Chen D, Sedivy J. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell. 2004;14:501-13 pubmed
    ..Distinct senescence programs can thus progress in parallel, resulting in mosaic cultures as well as individual cells responding to multiple signals. ..
  17. Laurberg J, Brems Eskildsen A, Nordentoft I, Fristrup N, Schepeler T, Ulhøi B, et al. Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int. 2012;110:E1228-36 pubmed publisher
    ..Here we use a large cohort of patients receiving radiotherapy to successfully validate the importance of MRE11 as a predictive marker of disease-specific survival (DSS)...
  18. Yuan S, Hou M, Hsieh Y, Huang C, Lee Y, Chen Y, et al. Role of MRE11 in cell proliferation, tumor invasion, and DNA repair in breast cancer. J Natl Cancer Inst. 2012;104:1485-502 pubmed publisher
    Previous studies have shown that altered forms of MRE11, a protein known to play a vital role in DNA double-strand break repair, DNA replication, and telomere maintenance are associated with cancer outcomes...
  19. Zhu X, Kuster B, Mann M, Petrini J, de Lange T. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet. 2000;25:347-52 pubmed
    ..Protein blotting showed that a small fraction of RAD50, MRE11 and the third component of the MRE11 double-strand break (DSB) repair complex, the Nijmegen breakage syndrome ..
  20. Carson C, Schwartz R, Stracker T, Lilley C, Lee D, Weitzman M. The Mre11 complex is required for ATM activation and the G2/M checkpoint. EMBO J. 2003;22:6610-20 pubmed
    ..It is unclear which proteins recognize DSBs and activate these pathways, but the Mre11/Rad50/NBS1 complex has been suggested to act as a damage sensor...
  21. Kobayashi J, Tauchi H, Sakamoto S, Nakamura A, Morishima K, Matsuura S, et al. NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain. Curr Biol. 2002;12:1846-51 pubmed
    ..Consequently, the FHA/BRCT domain is likely to have a crucial role for both binding to histone and for relocalization of hMRE11/hRAD50 nuclease complex to the vicinity of DNA damage. ..
  22. Ricceri F, Porcedda P, Allione A, Turinetto V, Polidoro S, Guarrera S, et al. Involvement of MRE11A and XPA gene polymorphisms in the modulation of DNA double-strand break repair activity: a genotype-phenotype correlation study. DNA Repair (Amst). 2011;10:1044-50 pubmed publisher
    ..005), while dephosphorylation was significantly higher in subjects carrying the variant allele in three MRE11A gene SNPs: rs1014666, rs476137 and rs2508784 (p-value=0.003, 0.003 and 0.008, respectively)...
  23. Olson E, Nievera C, Liu E, Lee A, Chen L, Wu X. The Mre11 complex mediates the S-phase checkpoint through an interaction with replication protein A. Mol Cell Biol. 2007;27:6053-67 pubmed
    The Mre11/Rad50/Nbs1 complex (MRN) plays an essential role in the S-phase checkpoint...
  24. Hopfner K, Karcher A, Craig L, Woo T, Carney J, Tainer J. Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase. Cell. 2001;105:473-85 pubmed
    To clarify functions of the Mre11/Rad50 (MR) complex in DNA double-strand break repair, we report Pyrococcus furiosus Mre11 crystal structures, revealing a protein phosphatase-like, dimanganese binding domain capped by a unique domain ..
  25. Stracker T, Carson C, Weitzman M. Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Nature. 2002;418:348-52 pubmed
    In mammalian cells, a conserved multiprotein complex of Mre11, Rad50 and NBS1 (also known as nibrin and p95) is important for double-strand break repair, meiotic recombination and telomere maintenance...
  26. Wang Y, Cortez D, Yazdi P, Neff N, Elledge S, Qin J. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 2000;14:927-39 pubmed
    ..This complex includes tumor suppressors and DNA damage repair proteins MSH2, MSH6, MLH1, ATM, BLM, and the RAD50-MRE11-NBS1 protein complex...
  27. Trujillo K, Yuan S, Lee E, Sung P. Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95. J Biol Chem. 1998;273:21447-50 pubmed
    Genetic studies in yeast have indicated a role of the RAD50 and MRE11 genes in homologous recombination, telomere length maintenance, and DNA repair processes...
  28. Ying S, Hamdy F, Helleday T. Mre11-dependent degradation of stalled DNA replication forks is prevented by BRCA2 and PARP1. Cancer Res. 2012;72:2814-21 pubmed publisher
    ..Here, we show increased levels of Mre11, a key component of MRN (Mre11-Rad50-Nbs1) complex that plays a role in the restart of stalled replication forks ..
  29. He J, Shi L, Truong L, Lu C, Razavian N, Li Y, et al. Rad50 zinc hook is important for the Mre11 complex to bind chromosomal DNA double-stranded breaks and initiate various DNA damage responses. J Biol Chem. 2012;287:31747-56 pubmed publisher
    The Mre11-Rad50-Nbs1 (MRN) complex plays critical roles in checkpoint activation and double-stranded break (DSB) repair...
  30. Buis J, Stoneham T, Spehalski E, Ferguson D. Mre11 regulates CtIP-dependent double-strand break repair by interaction with CDK2. Nat Struct Mol Biol. 2012;19:246-52 pubmed publisher
    ..S and G2 by cyclin-dependent kinase (CDK) phosphorylation of CtIP, which subsequently interacts with BRCA1 and the Mre11-Rad50-NBS1 (MRN) complex...
  31. Fukuda T, Sumiyoshi T, Takahashi M, Kataoka T, Asahara T, Inui H, et al. Alterations of the double-strand break repair gene MRE11 in cancer. Cancer Res. 2001;61:23-6 pubmed
    b>MRE11 plays a role in DNA double-strand break repair. Hypomorphic mutations of MRE11 have been demonstrated in ataxia-telangiectasia (AT)-like disorder...
  32. Rass E, Grabarz A, Plo I, Gautier J, Bertrand P, Lopez B. Role of Mre11 in chromosomal nonhomologous end joining in mammalian cells. Nat Struct Mol Biol. 2009;16:819-24 pubmed publisher
    ..We show that silencing Mre11 reduces the efficiency of nonhomologous end joining (NHEJ), affecting both the canonical and alternative pathways, ..
  33. Gaymes T, Mohamedali A, Patterson M, Matto N, Smith A, Kulasekararaj A, et al. Microsatellite instability induced mutations in DNA repair genes CtIP and MRE11 confer hypersensitivity to poly (ADP-ribose) polymerase inhibitors in myeloid malignancies. Haematologica. 2013;98:1397-406 pubmed publisher
    ..and primary samples (2 of 18, 11%) exhibited microsatellite instability with mono-allelic mutations in CtIP and MRE11. These changes were associated with reduced expression of mismatch repair pathway components, MSH2, MSH6 and MLH1...
  34. Robison J, Elliott J, Dixon K, Oakley G. Replication protein A and the Mre11.Rad50.Nbs1 complex co-localize and interact at sites of stalled replication forks. J Biol Chem. 2004;279:34802-10 pubmed
    ..a three subunit protein complex required for DNA replication and DNA repair) and the MRN complex (consisting of Mre11, Rad50, and Nbs1; involved in DNA double-strand break repair)...
  35. Huertas P, Cortes Ledesma F, Sartori A, Aguilera A, Jackson S. CDK targets Sae2 to control DNA-end resection and homologous recombination. Nature. 2008;455:689-92 pubmed publisher
    ..These findings therefore provide a mechanistic basis for cell-cycle control of DSB repair and highlight the importance of regulating DSB resection. ..
  36. Delia D, Piane M, Buscemi G, Savio C, Palmeri S, Lulli P, et al. MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia-telangiectasia-like disorder. Hum Mol Genet. 2004;13:2155-63 pubmed
    Hypomorphic mutations of the MRE11 gene are the hallmark of the radiosensitive ataxia-telangiectasia-like disorder (ATLD). Here, we describe a new family with two affected siblings, ATLD5 and ATLD6, now aged 37 and 36, respectively...
  37. Stewart G, Wang B, Bignell C, Taylor A, Elledge S. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature. 2003;421:961-6 pubmed
    ..These results highlight a crucial role for MDC1 in mediating transduction of the DNA damage signal. ..
  38. Pitts S, Kullar H, Stankovic T, Stewart G, Last J, Bedenham T, et al. hMRE11: genomic structure and a null mutation identified in a transcript protected from nonsense-mediated mRNA decay. Hum Mol Genet. 2001;10:1155-62 pubmed
    ..with a missense mutation inherited from their father, which is expressed as normal levels of partially functional MRE11 protein...
  39. Clynes D, Jelinska C, Xella B, Ayyub H, Taylor S, Mitson M, et al. ATRX dysfunction induces replication defects in primary mouse cells. PLoS ONE. 2014;9:e92915 pubmed publisher
    ..Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells...
  40. Price J, Pollock L, Rudd M, Fogoros S, Mohamed H, Hanigan C, et al. Sequencing of candidate chromosome instability genes in endometrial cancers reveals somatic mutations in ESCO1, CHTF18, and MRE11A. PLoS ONE. 2014;8:e63313 pubmed publisher
    ..We uncovered nonsynonymous somatic mutations in ESCO1, CHTF18, and MRE11A in, respectively, 3.7% (4 of 107), 1.9% (2 of 107), and 1.9% (2 of 107) of endometrial tumors. Overall, 7...
  41. Heikkinen K, Karppinen S, Soini Y, Makinen M, Winqvist R. Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility. J Med Genet. 2003;40:e131 pubmed
  42. Carney J, Maser R, Olivares H, Davis E, Le Beau M, Yates J, et al. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell. 1998;93:477-86 pubmed
    ..The implication of hMre11/hRad50/p95 protein complex in NBS reveals a direct molecular link between DSB repair and cell cycle checkpoint functions. ..
  43. Nimonkar A, Genschel J, Kinoshita E, Polaczek P, Campbell J, Wyman C, et al. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 2011;25:350-62 pubmed publisher
    ..human proteins: Bloom helicase (BLM); DNA2 helicase/nuclease; Exonuclease 1 (EXO1); the complex comprising MRE11, RAD50, and NBS1 (MRN); and Replication protein A (RPA). Resection occurs via two routes...
  44. Zhong Z, Jiang W, Cesare A, Neumann A, Wadhwa R, Reddel R. Disruption of telomere maintenance by depletion of the MRE11/RAD50/NBS1 complex in cells that use alternative lengthening of telomeres. J Biol Chem. 2007;282:29314-22 pubmed
    ..that overexpression of Sp100 protein can suppress ALT and that this was associated with sequestration of the MRE11/RAD50/NBS1 (MRN) recombination protein complex by Sp100...
  45. Ali Fehmi R, Chatterjee M, Ionan A, Levin N, Arabi H, Bandyopadhyay S, et al. Analysis of the expression of human tumor antigens in ovarian cancer tissues. Cancer Biomark. 2010;6:33-48 pubmed publisher
    ..and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC)...
  46. Rupnik A, Lowndes N, Grenon M. MRN and the race to the break. Chromosoma. 2010;119:115-35 pubmed publisher
    ..The MRN complex (MRX in yeast), composed of Mre11, Rad50 and Nbs1 (Xrs2), is a key component of the immediate early response to DNA damage, involved in a cross-talk ..
  47. Rollinson S, Kesby H, Morgan G. Haplotypic variation in MRE11, RAD50 and NBS1 and risk of non-Hodgkin's lymphoma. Leuk Lymphoma. 2006;47:2567-83 pubmed
    The MRE11-RAD50-NBS1 tri-complex is involved in the cellular response to DNA double strand breaks, detecting DNA damage, activating cell cycle checkpoints and apoptosis...
  48. Park Y, Chae J, Kim Y, Cho Y. Crystal structure of human Mre11: understanding tumorigenic mutations. Structure. 2011;19:1591-602 pubmed publisher
    b>Mre11 plays an important role in repairing damaged DNA by cleaving broken ends and by providing a platform for other DNA repair proteins. Various Mre11 mutations have been identified in several types of cancer...
  49. Vilar E, Bartnik C, Stenzel S, Raskin L, Ahn J, Moreno V, et al. MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. Cancer Res. 2011;71:2632-42 pubmed publisher
    ..generates mutations at repetitive DNA sequences such as those located in the double strand break (DSB) repair gene MRE11. We assessed the mutational status of MRE11 in a panel of 17 CRC cell lines and 46 primary tumors and found a ..
  50. Cheng W, Von Kobbe C, Opresko P, Arthur L, Komatsu K, Seidman M, et al. Linkage between Werner syndrome protein and the Mre11 complex via Nbs1. J Biol Chem. 2004;279:21169-76 pubmed
    ..The Nbs1 protein is mutated in Nijmegen breakage syndrome individuals and is part of the mammalian Mre11 complex together with the Mre11 and Rad50 proteins...
  51. Lee J, Paull T. ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science. 2005;308:551-4 pubmed
    ..We show that the Mre11-Rad50-Nbs1 (MRN) complex acts as a double-strand break sensor for ATM and recruits ATM to broken DNA molecules...
  52. Falck J, Coates J, Jackson S. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature. 2005;434:605-11 pubmed
  53. Giannini G, Ristori E, Cerignoli F, Rinaldi C, Zani M, Viel A, et al. Human MRE11 is inactivated in mismatch repair-deficient cancers. EMBO Rep. 2002;3:248-54 pubmed
    ..A related syndrome, the Ataxia-Telangiectasia-like disorder, is due to mutations of the MRE11 gene. However, the role of this gene in cancer development has not been established...
  54. Leung J, Ghosal G, Wang W, Shen X, Wang J, Li L, et al. Alpha thalassemia/mental retardation syndrome X-linked gene product ATRX is required for proper replication restart and cellular resistance to replication stress. J Biol Chem. 2013;288:6342-50 pubmed publisher
    ..In addition, we identified ATRX as a binding partner of MRE11-RAD50-NBS1 (MRN) complex...