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. 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 ..
  2. 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...
  3. 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...
  4. 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...
  5. 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. ..
  6. 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 ..
  7. 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...
  8. 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...
  9. 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...
  10. 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 ..

Detail Information

Publications95

  1. 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 ..
  2. 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...
  3. 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...
  4. 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...
  5. 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. ..
  6. 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 ..
  7. 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...
  8. 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...
  9. 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...
  10. 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 ..
  11. 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]...
  12. 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)...
  13. 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 ..
  14. 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...
  15. 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. ..
  16. 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 ..
  17. 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...
  18. 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 ..
  19. 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...
  20. 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...
  21. 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 ..
  22. 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...
  23. 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...
  24. 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 ..
  25. 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...
  26. 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 ..
  27. 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...
  28. 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...
  29. 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)...
  30. 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. ..
  31. 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...
  32. 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 ..
  33. 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 ..
  34. 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.
  35. 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 ..
  36. 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...
  37. 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...
  38. 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...
  39. 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 ..
  40. 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...
  41. 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...
  42. 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...
  43. 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...
  44. 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...
  45. 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 ..
  46. Seemanova E, Jarolim P, Seeman P, Varon R, Digweed M, Swift M, et al. Cancer risk of heterozygotes with the NBN founder mutation. J Natl Cancer Inst. 2007;99:1875-80 pubmed
    The autosomal recessive chromosomal instability disorder Nijmegen breakage syndrome (NBS) is associated with increased risk of lymphoid malignancies and other cancers. Cells from NBS patients contain many double-stranded DNA breaks...
  47. 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...
  48. 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...
  49. 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...
  50. Difilippantonio S, Celeste A, Kruhlak M, Lee Y, Difilippantonio M, Feigenbaum L, et al. Distinct domains in Nbs1 regulate irradiation-induced checkpoints and apoptosis. J Exp Med. 2007;204:1003-11 pubmed
    ..The NBS protein Nbs1 is not only a downstream target of AT mutated (ATM) kinase but also acts upstream, promoting optimal ATM activation,..
  51. Chen Y, Su Y, Chou P, Chiang W, Chang M, Wang L, et al. Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt. J Biol Chem. 2005;280:32505-11 pubmed
    ..The NBS gene product, NBS1 (p95) or nibrin, is a part of the hMre11 complex, a central player associated with double strand break repair...
  52. Stiff T, Reis C, Alderton G, Woodbine L, O Driscoll M, Jeggo P. Nbs1 is required for ATR-dependent phosphorylation events. EMBO J. 2005;24:199-208 pubmed
    ..b>Nbs1, the protein defective in NBS, functions in ataxia telangiectasia mutated protein (ATM)-dependent signalling likely ..
  53. 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...
  54. Millikan R, Player J, Decotret A, Tse C, Keku T. Polymorphisms in DNA repair genes, medical exposure to ionizing radiation, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2005;14:2326-34 pubmed
    ..break repair pathway: X-ray cross-complementing group 3 (XRCC3) codon 241 Thr/Met, Nijmegen breakage syndrome 1 (NBS1) codon 185 Glu/Gln, X-ray cross-complementing group 2 (XRCC2) codon 188 Arg/His, and breast cancer susceptibility ..
  55. 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)...
  56. Salewsky B, Wessendorf P, Hirsch D, Krenzlin H, Digweed M. Nijmegen breakage syndrome: the clearance pathway for mutant nibrin protein is allele specific. Gene. 2013;519:217-21 pubmed publisher
    ..disorder Nijmegen breakage syndrome (NBS) is caused by mutations in the NBN gene which codes for the protein nibrin (NBS1; p95)...
  57. Zhong Q, Chen C, Li S, Chen Y, Wang C, Xiao J, et al. Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. Science. 1999;285:747-50 pubmed
    ..Here, it is shown that BRCA1 interacts in vitro and in vivo with hRad50, which forms a complex with hMre11 and p95/nibrin. Upon irradiation, BRCA1 was detected in discrete foci in the nucleus, which colocalize with hRad50...
  58. Haince J, McDonald D, Rodrigue A, Déry U, Masson J, Hendzel M, et al. PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites. J Biol Chem. 2008;283:1197-208 pubmed
    ..Most importantly, we observed that the rapid accumulation of MRE11 and NBS1 at sites of DNA damage requires PARP1...
  59. Steffen J, Varon R, Mosor M, Maneva G, Maurer M, Stumm M, et al. Increased cancer risk of heterozygotes with NBS1 germline mutations in Poland. Int J Cancer. 2004;111:67-71 pubmed
    ..We found 15 carriers of the 657del5 mutation and 8 carriers of the R215W molecular variant of the NBS1 gene among 1,289 consecutive patients from Central Poland with various cancers and only 10 and 4 such carriers, ..
  60. 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...
  61. Roznowski K, Januszkiewicz Lewandowska D, Mosor M, Pernak M, Litwiniuk M, Nowak J. I171V germline mutation in the NBS1 gene significantly increases risk of breast cancer. Breast Cancer Res Treat. 2008;110:343-8 pubmed
    Nijmegen Breakage Syndrome (NBS) is a rare autosomal, recessive disease caused by homozygous mutations in the NBS1 gene...
  62. Matsuzaki K, Shinohara A, Shinohara M. 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. 2008;179:213-25 pubmed publisher
    ..Yeast Xrs2, a homolog of human Nbs1, is a component of the Mre11-Rad50-Xrs2 (MRX) complex required for both HR and NHEJ...
  63. Takai K, Sakamoto S, Sakai T, Yasunaga J, Komatsu K, Matsuoka M. A potential link between alternative splicing of the NBS1 gene and DNA damage/environmental stress. Radiat Res. 2008;170:33-40 pubmed publisher
    b>NBS1 forms a multimetric complex with MRE11/RAD50, which acts as the sensor of DNA double-strand breaks (DSBs). The mechanisms controlling the expression of NBS1 remain largely unknown...
  64. Cybulski C, Gorski B, Debniak T, Gliniewicz B, Mierzejewski M, Masojc B, et al. NBS1 is a prostate cancer susceptibility gene. Cancer Res. 2004;64:1215-9 pubmed
    To evaluate whether an inactivating mutation in the gene for the Nijmegen breakage syndrome (NBS1) plays a role in the etiology of prostate cancer, we compared the prevalence of the 657del5 NBS1 founder allele in 56 patients with familial ..
  65. Desai Mehta A, Cerosaletti K, Concannon P. Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization. Mol Cell Biol. 2001;21:2184-91 pubmed
    ..Nijmegen breakage syndrome (NBS) results from truncating mutations in the NBS1 gene, which encodes the protein nibrin. Nibrin is part of a nuclear multiprotein complex that also contains the DNA repair proteins Mre11 and Rad50...
  66. 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
    ..involves the activation of DNA repair and cell cycle regulatory proteins including the MRN (Mre11, Rad50, and Nbs1) complex and replication protein A (RPA)...
  67. Kobayashi J, Tauchi H, Chen B, Burma S, Bruma S, Tashiro S, et al. Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1. Biochem Biophys Res Commun. 2009;380:752-7 pubmed publisher
    ..Here, we show that ATM as well as NBS1 is recruited to damaged-chromatin in a gamma-H2AX-dependent manner...
  68. Ohnishi K, Scuric Z, Schiestl R, Okamoto N, Takahashi A, Ohnishi T. siRNA targeting NBS1 or XIAP increases radiation sensitivity of human cancer cells independent of TP53 status. Radiat Res. 2006;166:454-62 pubmed
    b>NBS1 is essential for the repair of radiation-induced DNA double-strand breaks (DSBs) in yeast and higher vertebrate cells...
  69. Broberg K, Bjork J, Paulsson K, Hoglund M, Albin M. Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer. Carcinogenesis. 2005;26:1263-71 pubmed
    ..metabolism of genotoxic carcinogens (EPHX1, GSTA1, GSTM1, GSTP1, GSTT1, NAT1, NAT2 and NQO1) or DNA repair (APE1, NBS1, XPC, XPD, XRCC1, XRCC3 and XRCC4), could modify the association between telomere length and cancer risk...
  70. 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
    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...
  71. Saidi A, Li T, Weih F, Concannon P, Wang Z. Dual functions of Nbs1 in the repair of DNA breaks and proliferation ensure proper V(D)J recombination and T-cell development. Mol Cell Biol. 2010;30:5572-81 pubmed publisher
    ..malignancy are hallmarks of the human disease Nijmegen breakage syndrome (NBS; OMIM 251260), which is caused by NBS1 mutations...
  72. Musak L, Soucek P, Vodickova L, Naccarati A, Halasova E, Polakova V, et al. Chromosomal aberrations in tire plant workers and interaction with polymorphisms of biotransformation and DNA repair genes. Mutat Res. 2008;641:36-42 pubmed publisher
    ..Binary logistic regression analysis revealed that frequencies of chromatid-type aberrations were modulated by NBS1 Glu185Gln (OR 4.26, 95%CI 1.38-13.14, P=0.012), and to a moderate extent, by XPD Lys751Gln (OR 0.16, 95%CI 0.02-1...
  73. Yang M, Chang S, Chiou S, Liu C, Chi C, Chen P, et al. Overexpression of NBS1 induces epithelial-mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer. Oncogene. 2007;26:1459-67 pubmed
    ..demonstrated that overexpression of the DNA double-strand break repair protein Nijmegen breakage syndrome 1 (NBS1) is a prognostic marker of advanced HNSCCs...
  74. Cerosaletti K, Wright J, Concannon P. Active role for nibrin in the kinetics of atm activation. Mol Cell Biol. 2006;26:1691-9 pubmed
    ..Atm activation is stimulated by expression of the Mre11/Rad50/nibrin complex...
  75. Festa F, Kumar R, Sanyal S, Undén B, Nordfors L, Lindholm B, et al. Basal cell carcinoma and variants in genes coding for immune response, DNA repair, folate and iron metabolism. Mutat Res. 2005;574:105-11 pubmed
    ..nucleotide polymorphisms (SNPs), IL-6-174G/C, -634G/C, and -597G/A; IL-10-1082G/A and -592C/A; IL-1beta-511C/T; NBS1 exon 5 Glu185Gln; XPC exon 15 Lys939Gln; XPD exon 23 Lys751Gln; XRCC1 exon 10 Arg399Gln; XRCC3 exon 7 Thr241Met; ..
  76. Tseng S, Chang C, Wu K, Teng S. Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1. J Biol Chem. 2005;280:39594-600 pubmed
    ..The NBS gene product, NBS1, is a component of the MRE11-RAD50-NBS1 (MRN) complex, a central player associated with double strand break (DSB) ..
  77. Porhanova N, Sokolenko A, Sherina N, Ponomariova D, Tkachenko N, Matsko D, et al. Ovarian cancer patient with germline mutations in both BRCA1 and NBN genes. Cancer Genet Cytogenet. 2008;186:122-4 pubmed publisher
  78. Wu X, Ranganathan V, Weisman D, Heine W, Ciccone D, O Neill T, et al. ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Nature. 2000;405:477-82 pubmed
    Nijmegen breakage syndrome (NBS) is characterized by extreme radiation sensitivity, chromosomal instability and cancer...
  79. Maser R, Mirzoeva O, Wells J, Olivares H, Williams B, Zinkel R, et al. Mre11 complex and DNA replication: linkage to E2F and sites of DNA synthesis. Mol Cell Biol. 2001;21:6006-16 pubmed
    We show that the Mre11 complex associates with E2F family members via the Nbs1 N terminus...
  80. Naka K, Ikeda K, Motoyama N. Recruitment of NBS1 into PML oncogenic domains via interaction with SP100 protein. Biochem Biophys Res Commun. 2002;299:863-71 pubmed
    ..b>NBS1, the protein responsible for NBS, forms a complex with MRE11 and RAD50, and plays a vital role in DNA repair, cell ..
  81. Gorski B, Cybulski C, Huzarski T, Byrski T, Gronwald J, Jakubowska A, et al. Breast cancer predisposing alleles in Poland. Breast Cancer Res Treat. 2005;92:19-24 pubmed
    ..In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these ..
  82. Howlett N, Scuric Z, D Andrea A, Schiestl R. Impaired DNA double strand break repair in cells from Nijmegen breakage syndrome patients. DNA Repair (Amst). 2006;5:251-7 pubmed
    Nijmegen breakage syndrome, caused by mutations in the NBS1 gene, is an autosomal recessive chromosomal instability disorder characterized by cancer predisposition...
  83. 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 ..
  84. Shiotani B, Nguyen H, Håkansson P, Maréchal A, Tse A, Tahara H, et al. Two distinct modes of ATR activation orchestrated by Rad17 and Nbs1. Cell Rep. 2013;3:1651-62 pubmed publisher
    ..despite its reliance on ATR and TopBP1, substantial RPA32 Ser33 phosphorylation occurs in a Rad17-independent but Nbs1-dependent manner in vivo and in vitro...
  85. Fnu S, Williamson E, De Haro L, BRENNEMAN M, Wray J, Shaheen M, et al. Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining. Proc Natl Acad Sci U S A. 2011;108:540-5 pubmed publisher
    ..This dimethylation of H3K36 improved the association of early DNA repair components, including NBS1 and Ku70, with the induced DSB, and enhanced DSB repair...
  86. Chen Y, Chiang H, Yang M, Chen P, Chang S, Teng S, et al. Activation of phosphoinositide 3-kinase by the NBS1 DNA repair protein through a novel activation motif. J Mol Med (Berl). 2008;86:401-12 pubmed publisher
    ..The NBS gene product p95 (also known as NBS1) is part of the Mre11-Rad50-Nbs1 complex, a central player associated with double-strand break repair...
  87. Chiang Y, Teng S, Su Y, Hsieh F, Wu K. c-Myc directly regulates the transcription of the NBS1 gene involved in DNA double-strand break repair. J Biol Chem. 2003;278:19286-91 pubmed
    ..The NBS gene product, NBS1 (p95 or nibrin), is a part of the hMre11 complex, a central player associated with double-strand break (DSB) repair...
  88. Bogdanova N, Schürmann P, Waltes R, Feshchenko S, Zalutsky I, Bremer M, et al. NBS1 variant I171V and breast cancer risk. Breast Cancer Res Treat. 2008;112:75-9 pubmed
    The NBS1/p95 protein has a pivotal role in the sensing and repair of chromosome breaks. A missense mutation in the NBS1 gene, I171V, has recently been associated with a ninefold increased risk of breast cancer in Polish patients...