Nbs1

Summary

Gene Symbol: Nbs1
Description: nibrin
Alias: AT-V1, AT-V2, ATV, NBS, NBS1, P95, nibrin, Nijmegen breakage syndrome 1 (nibrin), cell cycle regulatory protein p95, p95 protein of the MRE11/RAD50 complex
Species: human
Products:     Nbs1

Top Publications

  1. Buscemi G, Savio C, Zannini L, Miccichè F, Masnada D, Nakanishi M, et al. Chk2 activation dependence on Nbs1 after DNA damage. Mol Cell Biol. 2001;21:5214-22 pubmed
    ..Here we show that the ATM-dependent activation of Chk2 by gamma- radiation requires Nbs1, the gene product involved in the Nijmegen breakage syndrome (NBS), a disorder that shares with AT a variety of ..
  2. Iijima K, Muranaka C, Kobayashi J, Sakamoto S, Komatsu K, Matsuura S, et al. NBS1 regulates a novel apoptotic pathway through Bax activation. DNA Repair (Amst). 2008;7:1705-16 pubmed publisher
    ..The NBS1 protein is known to be a key regulator of DNA damage repair...
  3. Hebbring S, Fredriksson H, White K, Maier C, Ewing C, McDonnell S, et al. Role of the Nijmegen breakage syndrome 1 gene in familial and sporadic prostate cancer. Cancer Epidemiol Biomarkers Prev. 2006;15:935-8 pubmed
    The Nijmegen breakage syndrome 1 (NBS1) gene, which participates in DNA double strand break repair, has been postulated to be a susceptibility factor for a number of cancers, including prostate cancer...
  4. Resnick I, Kondratenko I, Pashanov E, Maschan A, Karachunsky A, Togoev O, et al. 657del5 mutation in the gene for Nijmegen breakage syndrome (NBS1) in a cohort of Russian children with lymphoid tissue malignancies and controls. Am J Med Genet A. 2003;120A:174-9 pubmed
    ..The gene mutated in NBS, NBS1, was recently cloned from its location on chromosome 8q21. The encoded protein, nibrin (p95), together with hMre11 and hRad50, is involved in the double-strand DNA break repair system...
  5. 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
    ..the third component of the MRE11 double-strand break (DSB) repair complex, the Nijmegen breakage syndrome protein (NBS1), is associated with TRF2...
  6. Yang M, Chiang W, Chou T, Chang S, Chen P, Teng S, et al. Increased NBS1 expression is a marker of aggressive head and neck cancer and overexpression of NBS1 contributes to transformation. Clin Cancer Res. 2006;12:507-15 pubmed
    ..We showed previously that c-MYC directly activates the expression of the DNA double-strand break repair gene NBS1, and NBS1 overexpression contributes to transformation...
  7. Debniak T, Gorski B, Cybulski C, Jakubowska A, Kurzawski G, Lener M, et al. Germline 657del5 mutation in the NBS1 gene in patients with malignant melanoma of the skin. Melanoma Res. 2003;13:365-70 pubmed
    ..we determined in what proportion of consecutive malignant melanoma (MM) cases the 657del5 mutation of exon 6 of the NBS1 gene can be detected and whether it is associated with the occurrence of MM...
  8. Hari F, Spycher C, Jungmichel S, Pavic L, Stucki M. A divalent FHA/BRCT-binding mechanism couples the MRE11-RAD50-NBS1 complex to damaged chromatin. EMBO Rep. 2010;11:387-92 pubmed publisher
    The MRE11-RAD50-NBS1 (MRN) complex accumulates at sites of DNA double-strand breaks in large chromatin domains flanking the lesion site...
  9. Silva J, Teixeira A, Lobo F, Mauricio J, Medeiros R. DNA repair system and prostate cancer progression: the role of NBS1 polymorphism (rs1805794). DNA Cell Biol. 2012;31:1182-6 pubmed publisher
    b>NBS1 plays an important role in the maintenance of genomic integrity, by being involved in cellular response to DNA damage...

More Information

Publications139 found, 100 shown here

  1. Cerosaletti K, Morrison V, Sabath D, Willerford D, Concannon P. Mutations and molecular variants of the NBS1 gene in non-Hodgkin lymphoma. Genes Chromosomes Cancer. 2002;35:282-6 pubmed
    ..The inherited disorders ataxia-telangiectasia and Nijmegen breakage syndrome are caused by mutations in the ATM and NBS1 genes, respectively, and are characterized by generalized genomic instability and a high incidence of lymphoid ..
  2. Lee J, Goodarzi A, Jeggo P, Paull T. 53BP1 promotes ATM activity through direct interactions with the MRN complex. EMBO J. 2010;29:574-85 pubmed publisher
    The Mre11/Rad50/Nbs1 (MRN) complex has a central function in facilitating activation of the ATM protein kinase at sites of DNA double-strand breaks (DSBs)...
  3. 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
  4. Sanyal S, Festa F, Sakano S, Zhang Z, Steineck G, Norming U, et al. Polymorphisms in DNA repair and metabolic genes in bladder cancer. Carcinogenesis. 2004;25:729-34 pubmed
    ..group G (XPG), X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3), Nijmegen breakage syndrome 1 (NBS1), cyclin D1, methylene-tetrahydrofolate reductase (MTHFR), NAD(P)H dehydrogenase quinone 1 (NQO1), H-ras and ..
  5. 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
    ..Here, we show that NBS1, the gene product defective in Nijmegen breakage syndrome (NBS), physically interacts with histone, rather than ..
  6. Kobayashi J, Okui M, Asaithamby A, Burma S, Chen B, Tanimoto K, et al. WRN participates in translesion synthesis pathway through interaction with NBS1. Mech Ageing Dev. 2010;131:436-44 pubmed publisher
    ..Here, we demonstrate that WRN rapidly forms discrete nuclear foci in an NBS1-dependent manner following DNA damage...
  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. Ebi H, Matsuo K, Sugito N, Suzuki M, Osada H, Tajima K, et al. Novel NBS1 heterozygous germ line mutation causing MRE11-binding domain loss predisposes to common types of cancer. Cancer Res. 2007;67:11158-65 pubmed
    DNA damage response (DDR) pathways maintain genomic stability. A 657del5 mutation of NBS1, a key DDR component, causing the rare cancer-predisposing Nijmegen breakage syndrome has been reported nearly exclusively in Slavic populations...
  9. Chailleux C, Tyteca S, Papin C, Boudsocq F, Puget N, Courilleau C, et al. Physical interaction between the histone acetyl transferase Tip60 and the DNA double-strand breaks sensor MRN complex. Biochem J. 2010;426:365-71 pubmed publisher
    ..indicating that Tip60 expression is necessary for the recruitment of the DNA damage sensor MRN (Mre11-Rad50-Nbs1) complex to DNA DSBs...
  10. Ciara E, Piekutowska Abramczuk D, Popowska E, Grajkowska W, Barszcz S, Perek D, et al. Heterozygous germ-line mutations in the NBN gene predispose to medulloblastoma in pediatric patients. Acta Neuropathol. 2010;119:325-34 pubmed publisher
    The NBN (NBS1) gene belongs to a group of double-strand break repair genes. Mutations in any of these genes cause genome instability syndromes and contribute to carcinogenesis...
  11. Laczmanska I, Gil J, Karpinski P, Stembalska A, Kozlowska J, Busza H, et al. Influence of polymorphisms in xenobiotic-metabolizing genes and DNA-repair genes on diepoxybutane-induced SCE frequency. Environ Mol Mutagen. 2006;47:666-73 pubmed
    ..GSTT1, EPHX, and NAT2), as well as DNA repair proteins (XRCC1, XRCC2, XRCC3, XPD, XPA, XPC, XPG, XPF, ERCC1, BRCA1, NBS1, and RAD51)...
  12. Mendez G, Cilli D, Berardinelli F, Viganotti M, Ascenzi P, Tanzarella C, et al. Cleavage of the BRCT tandem domains of nibrin by the 657del5 mutation affects the DNA damage response less than the Arg215Trp mutation. IUBMB Life. 2012;64:853-61 pubmed publisher
    ..The N-terminus of nibrin (NBN) contains a tandem breast cancer 1 (BRCA1) carboxy-terminal (BRCT) domain that represents one of the major ..
  13. Varon R, Vissinga C, Platzer M, Cerosaletti K, Chrzanowska K, Saar K, et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell. 1998;93:467-76 pubmed
    ..We describe the positional cloning of a gene encoding a novel protein, nibrin. It contains two modules found in cell cycle checkpoint proteins, a forkhead-associated domain adjacent to a ..
  14. Difilippantonio S, Celeste A, Fernandez Capetillo O, Chen H, Reina San Martin B, Van Laethem F, et al. Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models. Nat Cell Biol. 2005;7:675-85 pubmed
    ..Here we demonstrate that Nbs1-null B cells are defective in the activation of ataxia-telangiectasia-mutated (Atm) in response to ionizing ..
  15. Huen M, Grant R, Manke I, Minn K, Yu X, Yaffe M, et al. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell. 2007;131:901-14 pubmed
    ..Together, our study implicates RNF8 as a novel DNA-damage-responsive protein that integrates protein phosphorylation and ubiquitylation signaling and plays a critical role in the cellular response to genotoxic stress. ..
  16. Chrzanowska K, Piekutowska Abramczuk D, Popowska E, Gładkowska Dura M, Małdyk J, Syczewska M, et al. Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies. Int J Cancer. 2006;118:1269-74 pubmed
    ..Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with ..
  17. Varon R, Reis A, Henze G, von Einsiedel H, Sperling K, Seeger K. Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL). Cancer Res. 2001;61:3570-2 pubmed
    ..Mutations S93L, D95N, and I171V occur in the two known domains of nibrin that are probably involved in protein-protein interactions...
  18. Cerosaletti K, Concannon P. Nibrin forkhead-associated domain and breast cancer C-terminal domain are both required for nuclear focus formation and phosphorylation. J Biol Chem. 2003;278:21944-51 pubmed
    The Mre11.Rad50.nibrin protein complex plays an essential role in the mammalian cellular response to DNA double-strand breaks...
  19. 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)...
  20. Cerosaletti K, Concannon P. Independent roles for nibrin and Mre11-Rad50 in the activation and function of Atm. J Biol Chem. 2004;279:38813-9 pubmed
    The Atm protein kinase and Mre11-Rad50-nibrin (MRN) complex play an integral role in the cellular response to DNA double-strand breaks...
  21. Ziólkowska I, Mosor M, Wierzbicka M, Rydzanicz M, Pernak Schwarz M, Nowak J. Increased risk of larynx cancer in heterozygous carriers of the I171V mutation of the NBS1 gene. Cancer Sci. 2007;98:1701-5 pubmed
    ..Recent studies suggest that carriers of heterozygous mutations in the NBS1 gene have an increased risk of malignant tumor development...
  22. Shen M, Lan Q, Zhang L, Chanock S, Li G, Vermeulen R, et al. Polymorphisms in genes involved in DNA double-strand break repair pathway and susceptibility to benzene-induced hematotoxicity. Carcinogenesis. 2006;27:2083-9 pubmed
    ..We analyzed one or more single nucleotide polymorphisms (SNPs) in each of seven candidate genes (WRN, TP53, NBS1, BRCA1, BRCA2, XRCC3 and XRCC4) in a study of 250 workers exposed to benzene and 140 controls in China...
  23. Chapman J, Jackson S. Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage. EMBO Rep. 2008;9:795-801 pubmed publisher
    ..MDC1 interacts with several DDR proteins, including the MRE11-RAD50-NBS1 (MRN) complex...
  24. Gatei M, Young D, Cerosaletti K, Desai Mehta A, Spring K, Kozlov S, et al. ATM-dependent phosphorylation of nibrin in response to radiation exposure. Nat Genet. 2000;25:115-9 pubmed
    ..The protein defective in NBS, nibrin (encoded by NBS1), forms a complex with MRE11 and RAD50 (refs 1,2)...
  25. 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...
  26. Yazdi P, Wang Y, Zhao S, Patel N, Lee E, Qin J. SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev. 2002;16:571-82 pubmed
    ..Here we report that SMC1 is a component of the DNA damage response network that functions as an effector in the ATM/NBS1-dependent S-phase checkpoint pathway...
  27. Lan Q, Shen M, Berndt S, Bonner M, He X, Yeager M, et al. Smoky coal exposure, NBS1 polymorphisms, p53 protein accumulation, and lung cancer risk in Xuan Wei, China. Lung Cancer. 2005;49:317-23 pubmed
    ..The NBS1 gene product participates in DNA double-strand break repair and DNA damage-induced checkpoint activation, which are ..
  28. Hou Y, Toh M, Wang X. NBS1 deficiency promotes genome instability by affecting DNA damage signaling pathway and impairing telomere integrity. Cell Biochem Funct. 2012;30:233-42 pubmed publisher
    Studies revealed that Nijmegen Breakage Syndrome protein 1 (NBS1) plays an important role in maintaining genome stability, but the underlying mechanism is controversial and elusive...
  29. Nowak J, Mosor M, Ziółkowska I, Wierzbicka M, Pernak Schwarz M, Przyborska M, et al. Heterozygous carriers of the I171V mutation of the NBS1 gene have a significantly increased risk of solid malignant tumours. Eur J Cancer. 2008;44:627-30 pubmed publisher
    Homozygous mutation 657del5 within the NBS1 gene is responsible for the majority of Nijmegen breakage syndrome (NBS) cases. NBS patients are characterised by increased susceptibility to malignancies mainly of lymphoid origin...
  30. Yabuki M, Fujii M, Maizels N. The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions. Nat Immunol. 2005;6:730-6 pubmed
    ..MRE11-RAD50-NBS1 (MRN) is a ubiquitous and conserved nuclease complex critical for DNA break repair and is essential in class-switch ..
  31. Seemanova E, Sperling K, Neitzel H, Varon R, Hadac J, Butova O, et al. Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability. J Med Genet. 2006;43:218-24 pubmed
    ..arginine with the non-polar tryptophan and thus could potentially interfere with the function of the NBS1 protein, nibrin. Children with congenital microcephaly are routinely tested for the 657del5 mutation in the Czech and Slovak ..
  32. Zienolddiny S, Campa D, Lind H, Ryberg D, Skaug V, Stangeland L, et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis. 2006;27:560-7 pubmed
    ..OGG1, MPG, XRCC1, PCNA, POLB, POLiota, LIG3 and EXO1; double-strand break repair (DSB-R) genes XRCC2, XRCC3, XRCC9, NBS1 and ATR; and direct damage reversal (DR) gene MGMT/AGT...
  33. Falck J, Forment J, Coates J, Mistrik M, Lukas J, Bartek J, et al. CDK targeting of NBS1 promotes DNA-end resection, replication restart and homologous recombination. EMBO Rep. 2012;13:561-8 pubmed publisher
    The conserved MRE11–RAD50–NBS1 (MRN) complex is an important sensor of DNA double-strand breaks (DSBs) and facilitates DNA repair by homologous recombination (HR) and end joining...
  34. Kobayashi J, Antoccia A, Tauchi H, Matsuura S, Komatsu K. NBS1 and its functional role in the DNA damage response. DNA Repair (Amst). 2004;3:855-61 pubmed
    ..b>NBS1, the product of the gene underlying the disease, contains three functional regions: the forkhead-associated (FHA) ..
  35. Lins S, Kim R, Krüger L, Chrzanowska K, Seemanova E, Digweed M. Clinical variability and expression of the NBN c.657del5 allele in Nijmegen Breakage Syndrome. Gene. 2009;447:12-7 pubmed publisher
    ..by alternative translation, to varying amounts of a partially functional carboxy-terminal protein fragment, p70-nibrin. The expression level of p70-nibrin correlates with cancer incidence amongst patients...
  36. di Masi A, Viganotti M, Polticelli F, Ascenzi P, Tanzarella C, Antoccia A. The R215W mutation in NBS1 impairs gamma-H2AX binding and affects DNA repair: molecular bases for the severe phenotype of 657del5/R215W Nijmegen breakage syndrome patients. Biochem Biophys Res Commun. 2008;369:835-40 pubmed publisher
    ..The NBS1 protein, mutated in NBS patients, contains a FHA/BRCT domain necessary for the DNA-double strand break (DSB) damage ..
  37. 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
    ..Comparison of the p95 cDNA to the NBS1 cDNA indicated that the p95 gene and NBS1 are identical...
  38. Matsuura S, Tauchi H, Nakamura A, Kondo N, Sakamoto S, Endo S, et al. Positional cloning of the gene for Nijmegen breakage syndrome. Nat Genet. 1998;19:179-81 pubmed
    ..Here, we report the positional cloning of the NBS gene, NBS1, from an 800-kb candidate region. The gene comprises 50 kb and encodes a protein of 754 amino acids...
  39. 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...
  40. Heikkinen K, Rapakko K, Karppinen S, Erkko H, Knuutila S, Lundan T, et al. RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability. Carcinogenesis. 2006;27:1593-9 pubmed
    The Mre11 complex, composed of RAD50, NBS1 and MRE11, has an essential role in the maintenance of genomic integrity and preventing cells from malignancy...
  41. Park J, Park E, Lee H, Kim S, Hur S, Imbalzano A, et al. Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction. EMBO J. 2006;25:3986-97 pubmed
    ..Given the crucial role for gamma-H2AX in efficient DSB repair, these results suggest that the SWI/SNF complexes facilitate DSB repair, at least in part, by promoting H2AX phosphorylation by directly acting on chromatin. ..
  42. Lee J, Xu B, Lee C, Ahn J, Song M, Lee H, et al. Distinct functions of Nijmegen breakage syndrome in ataxia telangiectasia mutated-dependent responses to DNA damage. Mol Cancer Res. 2003;1:674-81 pubmed
    Phosphorylation of NBS1, the product of the gene mutated in Nijmegen breakage syndrome (NBS), by ataxia telangiectasia mutated (ATM), the product of the gene mutated in ataxia telangiectasia, is required for activation of the S phase ..
  43. Alt J, Bouska A, Fernandez M, Cerny R, Xiao H, Eischen C. Mdm2 binds to Nbs1 at sites of DNA damage and regulates double strand break repair. J Biol Chem. 2005;280:18771-81 pubmed
    ..Here we report the identification of a specific association of Mdm2 with Mre11, Nbs1, and Rad50, a DNA double strand break repair complex...
  44. 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...
  45. 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...
  46. Williams R, Dodson G, Limbo O, Yamada Y, Williams J, Guenther G, et al. Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair. Cell. 2009;139:87-99 pubmed publisher
    The Nijmegen breakage syndrome 1 (Nbs1) subunit of the Mre11-Rad50-Nbs1 (MRN) complex protects genome integrity by coordinating double-strand break (DSB) repair and checkpoint signaling through undefined interactions with ATM, MDC1, and ..
  47. Cybulski C, Wokołorczyk D, Kluźniak W, Jakubowska A, Gorski B, Gronwald J, et al. An inherited NBN mutation is associated with poor prognosis prostate cancer. Br J Cancer. 2013;108:461-8 pubmed publisher
    To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients...
  48. 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
    ..complex includes tumor suppressors and DNA damage repair proteins MSH2, MSH6, MLH1, ATM, BLM, and the RAD50-MRE11-NBS1 protein complex...
  49. Ranganathan V, Heine W, Ciccone D, Rudolph K, Wu X, Chang S, et al. Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit. Curr Biol. 2001;11:962-6 pubmed
    Nijmegen breakage syndrome (NBS) is a rare human disease displaying chromosome instability, radiosensitivity, cancer predisposition, immunodeficiency, and other defects [1, 2]...
  50. Kuschel B, Auranen A, McBride S, Novik K, Antoniou A, Lipscombe J, et al. Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet. 2002;11:1399-407 pubmed
    ..breast cancer case-control study analysing polymorphisms in genes involved in homologous recombination (NBS1, RAD52, RAD51, XRCC2 and XRCC3) and non-homologous end-joining (KU70/80 and LIG4)...
  51. 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. ..
  52. Horejsi Z, Falck J, Bakkenist C, Kastan M, Lukas J, Bartek J. Distinct functional domains of Nbs1 modulate the timing and magnitude of ATM activation after low doses of ionizing radiation. Oncogene. 2004;23:3122-7 pubmed
    ..phosphorylation after exposure of human fibroblasts to low doses (2 Gy) of IR are altered in cells deficient in Nbs1, a substrate of ATM and a component of the MRN (Mre11-Rad50-Nbs1) complex involved in processing/repair of DSBs and ..
  53. 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 between the ..
  54. Huang J, Grotzer M, Watanabe T, Hewer E, Pietsch T, Rutkowski S, et al. Mutations in the Nijmegen breakage syndrome gene in medulloblastomas. Clin Cancer Res. 2008;14:4053-8 pubmed publisher
    ..Nijmegen breakage syndrome (NBS) with NBS1 germ-line mutations is a rare autosomal recessive disease with clinical features that include microcephaly, mental ..
  55. Hematulin A, Sagan D, Eckardt Schupp F, Moertl S. NBS1 is required for IGF-1 induced cellular proliferation through the Ras/Raf/MEK/ERK cascade. Cell Signal. 2008;20:2276-85 pubmed publisher
    b>NBS1 is a member of the Mre11-Rad50-NBS1 complex, which plays a role in cellular responses to DNA damage and the maintenance of genomic stability...
  56. 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...
  57. Forsti A, Angelini S, Festa F, Sanyal S, Zhang Z, Grzybowska E, et al. Single nucleotide polymorphisms in breast cancer. Oncol Rep. 2004;11:917-22 pubmed
    ..The frequencies for single nucleotide polymorphisms (SNPs) were measured in the following genes: NBS1, XPC, XPD, XRCC1, XRCC3, MTHFR, and cyclin D1. Odds ratios (ORs) were calculated to the wild-type genotype...
  58. Laczmanska I, Gil J, Karpinski P, Stembalska A, Trusewicz A, Pesz K, et al. Polymorphism in nucleotide excision repair gene XPC correlates with bleomycin-induced chromosomal aberrations. Environ Mol Mutagen. 2007;48:666-71 pubmed
    ..of DNA repair such as: XRCC1 [base excision repair]; XPA, XPC, XPG, XPD, XPF, ERCC1 [nucleotide excision repair], NBS1, RAD51, XRCC2, XRCC3, RAD51, and BRCA1 [homologous recombination], as well as in genes encoding xenobiotic ..
  59. Bogdanova N, Feshchenko S, Schürmann P, Waltes R, Wieland B, Hillemanns P, et al. Nijmegen Breakage Syndrome mutations and risk of breast cancer. Int J Cancer. 2008;122:802-6 pubmed
    Mutations in the NBS1 gene have been identified as disease-causing mutations in patients with Nijmegen Breakage Syndrome (NBS), but their clinical impact on breast cancer susceptibility has remained uncertain...
  60. Zhao S, Renthal W, Lee E. Functional analysis of FHA and BRCT domains of NBS1 in chromatin association and DNA damage responses. Nucleic Acids Res. 2002;30:4815-22 pubmed
    Rad50/Mre11/NBS1 (R/M/N) is a multi-functional protein complex involved in DNA repair, cell cycle checkpoint activation, DNA replication and replication block-induced responses...
  61. Figueroa J, Malats N, Rothman N, Real F, Silverman D, Kogevinas M, et al. Evaluation of genetic variation in the double-strand break repair pathway and bladder cancer risk. Carcinogenesis. 2007;28:1788-93 pubmed
    ..single-nucleotide polymorphisms (SNPs) in seven candidate genes whose products are involved in DNA break sensing (NBS1, BRCA1 interacting genes BRIP1 and ZNF350), non-homologous end-joining (NHEJ) DNA repair (XRCC4) and homologous ..
  62. 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...
  63. Melander F, Bekker Jensen S, Falck J, Bartek J, Mailand N, Lukas J. Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin. J Cell Biol. 2008;181:213-26 pubmed publisher
    DNA double-strand breaks (DSBs) trigger accumulation of the MRE11-RAD50-Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on the DSB-flanking chromatin facilitates survival...
  64. Sakamoto S, Iijima K, Mochizuki D, Nakamura K, Teshigawara K, Kobayashi J, et al. Homologous recombination repair is regulated by domains at the N- and C-terminus of NBS1 and is dissociated with ATM functions. Oncogene. 2007;26:6002-9 pubmed
    The proteins responsible for radiation sensitive disorders, NBS1, kinase ataxia-telangiectasia-(A-T)-mutated (ATM) and MRE11, interact through the C-terminus of NBS1 in response to the generation of DNA double-strand breaks (DSBs) and are ..
  65. Zhao S, Weng Y, Yuan S, Lin Y, Hsu H, Lin S, et al. Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products. Nature. 2000;405:473-7 pubmed
    ..The NBS1 protein is specifically mutated in patients with Nijmegen breakage syndrome and forms a complex with the DNA repair ..
  66. Plisiecka Hałasa J, Dansonka Mieszkowska A, Rembiszewska A, Bidzinski M, Steffen J, Kupryjanczyk J. Nijmegen breakage syndrome gene (NBS1) alterations and its protein (nibrin) expression in human ovarian tumours. Ann Hum Genet. 2002;66:353-9 pubmed
    We looked for NBS1 gene (602667) alterations and changes in nibrin expression in 162 human gynaecological tumours, mostly ovarian. Exons 6-8 and 10 of the NBS1 gene were evaluated by the SSCP and direct sequencing method...
  67. Ryk C, Kumar R, Thirumaran R, Hou S. Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk for lung cancer in never- and ever-smokers. Lung Cancer. 2006;54:285-92 pubmed
    ..repair (BER) genes, XRCC1 and APEX1 and two genes involved in homologous recombination repair (HR), XRCC3 and NBS1. Never-smoking lung cancer patients were recruited, and also the next diagnosed ever-smoking case of the same ..
  68. Chen L, Nievera C, Lee A, Wu X. Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair. J Biol Chem. 2008;283:7713-20 pubmed publisher
    ..Here we describe that BRCA1 forms a complex with CtIP and MRN (Mre11/Rad50/Nbs1) in a cell cycle-dependent manner...
  69. Zhang L, Zhang Z, Yan W. Single nucleotide polymorphisms for DNA repair genes in breast cancer patients. Clin Chim Acta. 2005;359:150-5 pubmed
    ..SSCP and RFLP were used to analyze genotypes of DNA repair genes for NBS1, XPC, XPD and XRCC3. T/C in XRCC3 exon 7 had a somewhat deviation from HWE in BC group (P=0.08)...
  70. Lu J, Wei Q, Bondy M, Li D, Brewster A, Shete S, et al. Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <or=55 years. Carcinogenesis. 2006;27:2209-16 pubmed
    ..Nijmegen breakage syndrome 1 (NBS1) protein is one of the key proteins that participates in recognition and repair of DSBs in humans...
  71. 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
    ..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...
  72. Wen J, Cerosaletti K, Schultz K, Wright J, Concannon P. NBN phosphorylation regulates the accumulation of MRN and ATM at sites of DNA double-strand breaks. Oncogene. 2013;32:4448-56 pubmed publisher
    ..These data indicate that following the induction of DSBs, phosphorylation of NBN regulates its accumulation, and that of ATM, at sites of DNA DSB as well as the timing of the repair of these sites. ..
  73. 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 ..
  74. Lee J, Paull T. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science. 2004;304:93-6 pubmed
    The complex containing the Mre11, Rad50, and Nbs1 proteins (MRN) is essential for the cellular response to DNA double-strand breaks, integrating DNA repair with the activation of checkpoint signaling through the protein kinase ATM (ataxia ..
  75. Digweed M, Sperling K. Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks. DNA Repair (Amst). 2004;3:1207-17 pubmed
    ..The underlying gene, NBS1, is located on human chromosome 8q21 and codes for a protein product termed nibrin, Nbs1 or p95...
  76. 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
    ..Here we identify related, conserved carboxy-terminal motifs in human Nbs1, ATRIP and Ku80 proteins that are required for their interaction with ATM, ATR and DNA-PKcs, respectively...
  77. Berkovich E, Monnat R, Kastan M. Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nat Cell Biol. 2007;9:683-90 pubmed
    ..The detection of human ATM protein at site-specific DSBs required functional NBS1 protein, ATM kinase activity and ATM autophosphorylation on Ser 1981...
  78. Wu L, Luo K, Lou Z, Chen J. MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks. Proc Natl Acad Sci U S A. 2008;105:11200-5 pubmed publisher
    The product of the Nijmegen breakage syndrome gene (NBS1) plays crucial roles in DNA damage response through its association with many proteins, including MRE11 and RAD50...
  79. Antoccia A, Sakamoto S, Matsuura S, Tauchi H, Komatsu K. NBS1 prevents chromatid-type aberrations through ATM-dependent interactions with SMC1. Radiat Res. 2008;170:345-52 pubmed publisher
    ..We show here that after irradiation, NBS1 interacts physically with both BRCA1 and SMC1, a component of the cohesin complex, and that their interactions are ..
  80. Sagan D, Müller R, Kröger C, Hematulin A, Mörtl S, Eckardt Schupp F. The DNA repair protein NBS1 influences the base excision repair pathway. Carcinogenesis. 2009;30:408-15 pubmed publisher
    b>NBS1 fulfills important functions for the maintenance of genomic stability and cellular survival. Mutations in the NBS1 (Nijmegen Breakage Syndrome 1) gene are responsible for the Nijmegen breakage syndrome (NBS) in humans...
  81. Watanabe T, Nobusawa S, Lu S, Huang J, Mittelbronn M, Ohgaki H. Mutational inactivation of the nijmegen breakage syndrome gene (NBS1) in glioblastomas is associated with multiple TP53 mutations. J Neuropathol Exp Neurol. 2009;68:210-5 pubmed publisher
    Nijmegen breakage syndrome caused by NBS1 germline mutations is a rare autosomal recessive disease with clinical features that include microcephaly, increased radiosensitivity, and predisposition to cancer...
  82. Rodier F, Coppe J, Patil C, Hoeijmakers W, Muñoz D, Raza S, et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 2009;11:973-9 pubmed publisher
    ..Initiation and maintenance of this cytokine response required the DDR proteins ATM, NBS1 and CHK2, but not the cell-cycle arrest enforcers p53 and pRb...
  83. Yuan J, Chen J. N terminus of CtIP is critical for homologous recombination-mediated double-strand break repair. J Biol Chem. 2009;284:31746-52 pubmed publisher
    ..CtIP (also known as RBBP8) acts together with the MRN (MRE11-RAD50-NBS1) complex to promote DNA end resection and the generation of single-stranded DNA, which is critically important for ..
  84. Lloyd J, Chapman J, Clapperton J, Haire L, Hartsuiker E, Li J, et al. A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage. Cell. 2009;139:100-11 pubmed publisher
    The Mre11/Rad50/Nbs1 protein complex plays central enzymatic and signaling roles in the DNA-damage response...
  85. 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
    ..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...
  86. 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. Together, these results suggest a non-canonical function of ATRX in guarding genomic stability.
  87. 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
    ..of human Rad50, Mre11, and another protein factor with a size of about 95 kDa (p95), which is likely to be Nibrin, the protein encoded by the gene mutated in Nijmegen breakage syndrome...
  88. Chen H, Bhandoola A, Difilippantonio M, Zhu J, Brown M, Tai X, et al. Response to RAG-mediated VDJ cleavage by NBS1 and gamma-H2AX. Science. 2000;290:1962-5 pubmed
    ..We report that the Nijmegen breakage syndrome protein (NBS1) and histone gamma-H2AX, which associate with irradiation-induced DNA double-strand breaks (DSBs), are also found ..
  89. Goode E, Dunning A, Kuschel B, Healey C, Day N, Ponder B, et al. Effect of germ-line genetic variation on breast cancer survival in a population-based study. Cancer Res. 2002;62:3052-7 pubmed
    ..No effect on survival was seen for polymorphisms in ATM, BRCA1/2, CHK2, KU70, NBS1, RAD51, RAD52, XRCC3, AR, COMT, NQO1, VDR, ADH3, CYP1A1, GSTP1, TGF-beta, or CDH1...
  90. Medina P, Ahrendt S, Pollan M, Fernandez P, Sidransky D, Sanchez Cespedes M. Screening of homologous recombination gene polymorphisms in lung cancer patients reveals an association of the NBS1-185Gln variant and p53 gene mutations. Cancer Epidemiol Biomarkers Prev. 2003;12:699-704 pubmed
    ..Nonsynonymous polymorphisms with a frequency higher that 0.1 at the XRCC3, NBS1, and BRCA2 genes were selected for the study...
  91. 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
    ..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)...
  92. Buslov K, Iyevleva A, Chekmariova E, Suspitsin E, Togo A, Kuligina E, et al. NBS1 657del5 mutation may contribute only to a limited fraction of breast cancer cases in Russia. Int J Cancer. 2005;114:585-9 pubmed
    The gene for Nijmegen chromosomal breakage syndrome (NBS1) plays a role in a variety of processes protecting chromosomal stability...