Nbn

Summary

Gene Symbol: Nbn
Description: nibrin
Alias: Nbs1, nibrin, cell cycle regulatory protein p95, nijmegen breakage syndrome protein 1 homolog
Species: mouse
Products:     Nbn

Top Publications

  1. Kracker S, Bergmann Y, Demuth I, Frappart P, Hildebrand G, Christine R, et al. Nibrin functions in Ig class-switch recombination. Proc Natl Acad Sci U S A. 2005;102:1584-9 pubmed
    ..NBS is caused by a hypomorphic mutation of the NBS1 gene, encoding nibrin, which forms a protein complex with Mre11 and Rad50, both involved in DNA repair...
  2. Kang J, Bronson R, Xu Y. Targeted disruption of NBS1 reveals its roles in mouse development and DNA repair. EMBO J. 2002;21:1447-55 pubmed
    ..The gene product mutated in NBS, named NBS1, is a component of the Mre11 complex that is involved in DNA strand-break repair...
  3. Deriano L, Stracker T, Baker A, Petrini J, Roth D. Roles for NBS1 in alternative nonhomologous end-joining of V(D)J recombination intermediates. Mol Cell. 2009;34:13-25 pubmed publisher
    ..Because the MRE11/RAD50/NBS1 complex localizes to RAG-mediated DSBs and possesses DNA end tethering, processing, and joining activities, we ..
  4. Yang Y, Frappart P, Frappart L, Wang Z, Tong W. A novel function of DNA repair molecule Nbs1 in terminal differentiation of the lens fibre cells and cataractogenesis. DNA Repair (Amst). 2006;5:885-93 pubmed
    The Nbs1 protein, hypomorphic mutant in Nijmegen breakage syndrome (NBS), is a component of the Mre11/Rad50/Nbs1 (M/R/N) complex that acts as a DNA double-strand break sensor and functions in cell cycle checkpoint in response to DNA ..
  5. Frappart P, Tong W, Demuth I, Radovanovic I, Herceg Z, Aguzzi A, et al. An essential function for NBS1 in the prevention of ataxia and cerebellar defects. Nat Med. 2005;11:538-44 pubmed
    ..Here we show that inactivation of the Nbn gene (also known as Nbs1) in mouse neural tissues results in a combination of the neurological anomalies characteristic of NBS, ataxia ..
  6. Li R, Yang Y, Gao Y, Wang Z, Tong W. A distinct response to endogenous DNA damage in the development of Nbs1-deficient cortical neurons. Cell Res. 2012;22:859-72 pubmed publisher
    Microcephaly is a clinical characteristic for human nijmegen breakage syndrome (NBS, mutated in NBS1 gene), a chromosomal instability syndrome. However, the underlying molecular pathogenesis remains elusive...
  7. Difilippantonio S, Gapud E, Wong N, Huang C, Mahowald G, Chen H, et al. 53BP1 facilitates long-range DNA end-joining during V(D)J recombination. Nature. 2008;456:529-33 pubmed publisher
    ..These data suggest a more general role for 53BP1 in maintaining genomic stability during long-range joining of DNA breaks. ..
  8. 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,..
  9. Zhou Z, Bruhn C, Wang Z. Differential function of NBS1 and ATR in neurogenesis. DNA Repair (Amst). 2012;11:210-21 pubmed publisher
    ..Mutations of NBS1 and ATR cause human genomic instability syndrome NBS and ATR-Seckel, respectively, both of which feature ..

More Information

Publications73

  1. Helmink B, Bredemeyer A, Lee B, Huang C, Sharma G, Walker L, et al. MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaks. J Exp Med. 2009;206:669-79 pubmed publisher
    The Mre11-Rad50-Nbs1 (MRN) complex functions in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) at postreplicative stages of the cell cycle...
  2. Shull E, Lee Y, Nakane H, Stracker T, Zhao J, Russell H, et al. Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS. Genes Dev. 2009;23:171-80 pubmed publisher
    The MRN complex (Mre11/RAD50/NBS1) and ATM (ataxia telangiectasia, mutated) are critical for the cellular response to DNA damage...
  3. Stracker T, Morales M, Couto S, Hussein H, Petrini J. The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11 complex. Nature. 2007;447:218-21 pubmed
    The MRE11 complex (MRE11, RAD50 and NBS1) and the ataxia-telangiectasia mutated (ATM) kinase function in the same DNA damage response pathway to effect cell cycle checkpoint activation and apoptosis...
  4. Reina San Martin B, Nussenzweig M, Nussenzweig A, Difilippantonio S. Genomic instability, endoreduplication, and diminished Ig class-switch recombination in B cells lacking Nbs1. Proc Natl Acad Sci U S A. 2005;102:1590-5 pubmed
    Mre11, Rad50, and Nbs1 form an evolutionarily conserved protein complex (Mre11-Rad50-Nbs1, MRN) that has been proposed to function as a DNA damage sensor...
  5. Kang J, Ferguson D, Song H, Bassing C, Eckersdorff M, Alt F, et al. Functional interaction of H2AX, NBS1, and p53 in ATM-dependent DNA damage responses and tumor suppression. Mol Cell Biol. 2005;25:661-70 pubmed
    ..H2AX, NBS1, and p53 are substrates of ATM kinase and are involved in ATM-dependent DNA damage responses...
  6. Kitagawa R, Bakkenist C, McKinnon P, Kastan M. Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev. 2004;18:1423-38 pubmed
    ..Here, we show that NBS1 and BRCA1 are required for the recruitment of previously activated ATM to the sites of DNA breaks after ionizing ..
  7. Wilda M, Demuth I, Concannon P, Sperling K, Hameister H. Expression pattern of the Nijmegen breakage syndrome gene, Nbs1, during murine development. Hum Mol Genet. 2000;9:1739-44 pubmed
    ..At the cellular level, NBS has some features in common with ataxia teleangiectasia. In this study the murine Nbs1 gene was used for an expression study in mouse embryos at different developmental stages as well as in adult mice...
  8. Theunissen J, Kaplan M, Hunt P, Williams B, Ferguson D, Alt F, et al. Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. Mol Cell. 2003;12:1511-23 pubmed
    ..We propose that in Mre11(ATLD1/ATLD1) mice, genome instability and cell cycle checkpoint defects reduce viability in early embryos and in proliferating cells, while promoting malignancy in the context of an initiating lesion. ..
  9. Ramiro A, Jankovic M, Callen E, Difilippantonio S, Chen H, McBride K, et al. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature. 2006;440:105-9 pubmed
    ..In addition, translocations are inhibited by the tumour suppressors ATM, Nbs1, p19 (Arf) and p53, which is consistent with activation of DNA damage- and oncogenic stress-induced checkpoints ..
  10. Cherry S, Adelman C, Theunissen J, Hassold T, Hunt P, Petrini J. The Mre11 complex influences DNA repair, synapsis, and crossing over in murine meiosis. Curr Biol. 2007;17:373-8 pubmed
    The Mre11 complex (consisting of MRE11, RAD50, and NBS1/Xrs2) is required for double-strand break (DSB) formation, processing, and checkpoint signaling during meiotic cell division in S. cerevisiae...
  11. Dumon Jones V, Frappart P, Tong W, Sajithlal G, Hulla W, Schmid G, et al. Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis. Cancer Res. 2003;63:7263-9 pubmed
    ..Southern and Western blot analyses showed a remaining wild-type allele and nibrin expression in Nbn(+/-) tumors. Sequencing analysis confirmed no mutation in the Nbn cDNA derived from these tumors...
  12. Buis J, Wu Y, Deng Y, Leddon J, Westfield G, Eckersdorff M, et al. Mre11 nuclease activity has essential roles in DNA repair and genomic stability distinct from ATM activation. Cell. 2008;135:85-96 pubmed publisher
    The Mre11/Rad50/NBS1 (MRN) complex maintains genomic stability by bridging DNA ends and initiating DNA damage signaling through activation of the ATM kinase...
  13. Baranes K, Raz Prag D, Nitzan A, Galron R, Ashery Padan R, Rotenstreich Y, et al. Conditional inactivation of the NBS1 gene in the mouse central nervous system leads to neurodegeneration and disorganization of the visual system. Exp Neurol. 2009;218:24-32 pubmed publisher
    ..NBS) is a genomic instability disease caused by hypomorphic mutations in the NBS1 gene encoding the Nbs1 (nibrin) protein...
  14. Celeste A, Fernandez Capetillo O, Kruhlak M, Pilch D, Staudt D, Lee A, et al. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol. 2003;5:675-9 pubmed
    ..Despite their initial recruitment to DSBs, numerous factors, including Nbs1, 53BP1 and Brca1, subsequently fail to form IRIF...
  15. Yang Y, Saidi A, Frappart P, Min W, Barrucand C, Dumon Jones V, et al. Conditional deletion of Nbs1 in murine cells reveals its role in branching repair pathways of DNA double-strand breaks. EMBO J. 2006;25:5527-38 pubmed
    b>NBS1 forms a complex with MRE11 and RAD50 (MRN) that is proposed to act on the upstream of two repair pathways of DNA double-strand break (DSB), homologous repair (HR) and non-homologous end joining (NHEJ)...
  16. Williams B, Mirzoeva O, Morgan W, Lin J, Dunnick W, Petrini J. A murine model of Nijmegen breakage syndrome. Curr Biol. 2002;12:648-53 pubmed
    ..NBS is caused by mutation of the NBS1 gene, which encodes a member of the Mre11 complex, a trimeric protein complex also containing Mre11 and Rad50...
  17. Tauchi H, Kobayashi J, Morishima K, Matsuura S, Nakamura A, Shiraishi T, et al. The forkhead-associated domain of NBS1 is essential for nuclear foci formation after irradiation but not essential for hRAD50[middle dot]hMRE11[middle dot]NBS1 complex DNA repair activity. J Biol Chem. 2001;276:12-5 pubmed
    b>NBS1 (p95), the protein responsible for Nijmegen breakage syndrome, shows a weak homology to the yeast Xrs2 protein at the N terminus region, known as the forkhead-associated (FHA) domain and the BRCA1 C terminus domain...
  18. Dar I, Yosha G, Elfassy R, Galron R, Wang Z, Shiloh Y, et al. Investigation of the functional link between ATM and NBS1 in the DNA damage response in the mouse cerebellum. J Biol Chem. 2011;286:15361-76 pubmed publisher
    ..The NBS1 protein that is defective in NBS is a component of the Mre11/RAD50/NBS1 (MRN) complex, which plays a major role in ..
  19. Zhu J, Petersen S, Tessarollo L, Nussenzweig A. Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice. Curr Biol. 2001;11:105-9 pubmed
    ..Recently, it was demonstrated that this chromosomal breakage syndrome is caused by mutations in the NBS1 gene that result in a total loss of full-length NBS1 expression...
  20. 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 ..
  21. Demuth I, Frappart P, Hildebrand G, Melchers A, Lobitz S, Stockl L, et al. An inducible null mutant murine model of Nijmegen breakage syndrome proves the essential function of NBS1 in chromosomal stability and cell viability. Hum Mol Genet. 2004;13:2385-97 pubmed
    ..The NBS1 gene codes for a protein, nibrin, involved in the processing/repair of DNA double strand breaks and in cell cycle checkpoints...
  22. Lee Y, Katyal S, Downing S, Zhao J, Russell H, McKinnon P. Neurogenesis requires TopBP1 to prevent catastrophic replicative DNA damage in early progenitors. Nat Neurosci. 2012;15:819-26 pubmed publisher
    ..Thus, TopBP1 is crucial for maintaining genome integrity in the early progenitors that drive neurogenesis. ..
  23. Rocha P, Raviram R, Fu Y, Kim J, Luo V, Aljoufi A, et al. A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination. Cell Rep. 2016;16:48-55 pubmed publisher
    ..Finally, our results explain how changes in Igh architecture in the absence of 53BP1 could promote inversional rearrangements that compromise CSR. ..
  24. Prochazkova J, Sakaguchi S, Owusu M, Mazouzi A, Wiedner M, Velimezi G, et al. DNA Repair Cofactors ATMIN and NBS1 Are Required to Suppress T Cell Activation. PLoS Genet. 2015;11:e1005645 pubmed publisher
    ..The DNA double-strand break signaling kinase ATM and its cofactor NBS1 are required during T cell development and for the maintenance of genomic stability...
  25. Rai R, Hu C, Broton C, Chen Y, Lei M, Chang S. NBS1 Phosphorylation Status Dictates Repair Choice of Dysfunctional Telomeres. Mol Cell. 2017;65:801-817.e4 pubmed publisher
    Telomeres employ TRF2 to protect chromosome ends from activating the DNA damage sensor MRE11-RAD50-NBS1 (MRN), thereby repressing ATM-dependent DNA damage checkpoint responses...
  26. Halberg R, Waggoner J, Rasmussen K, White A, Clipson L, Prunuske A, et al. Long-lived Min mice develop advanced intestinal cancers through a genetically conservative pathway. Cancer Res. 2009;69:5768-75 pubmed publisher
    ..we generated Apc(Min/+) mice homozygous for the hypomorphic allele of the Nijmegen breakage syndrome gene (Nbs1(DeltaB)) and also treated Apc(Min/+) mice with a strong somatic mutagen...
  27. 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...
  28. Spycher C, Miller E, Townsend K, Pavic L, Morrice N, Janscak P, et al. Constitutive phosphorylation of MDC1 physically links the MRE11-RAD50-NBS1 complex to damaged chromatin. J Cell Biol. 2008;181:227-40 pubmed publisher
    The MRE11-RAD50-Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex accumulates at sites of DNA double-strand breaks (DSBs) in microscopically discernible nuclear foci...
  29. Shimada M, Sagae R, Kobayashi J, Habu T, Komatsu K. Inactivation of the Nijmegen breakage syndrome gene leads to excess centrosome duplication via the ATR/BRCA1 pathway. Cancer Res. 2009;69:1768-75 pubmed publisher
    ..Nijmegen breakage syndrome 1 (NBS1), the protein which is mutated in these patients, functions in association with BRCA1 and ATR as part of the ..
  30. Bouska A, Lushnikova T, Plaza S, Eischen C. Mdm2 promotes genetic instability and transformation independent of p53. Mol Cell Biol. 2008;28:4862-74 pubmed publisher
    ..breaks and delayed DNA double-strand break repair in cells lacking p53 but not in cells with a mutant form of Nbs1, a component of the Mre11/Rad50/Nbs1 DNA repair complex...
  31. Gupta G, Vanness K, Barlas A, Manova Todorova K, Wen Y, Petrini J. The Mre11 complex suppresses oncogene-driven breast tumorigenesis and metastasis. Mol Cell. 2013;52:353-65 pubmed publisher
    ..These findings provide insight into the mechanism of DDR engagement by activated oncogenes and highlight genetic interactions between the DDR and Ink4a-Arf pathways in suppression of oncogene-driven tumorigenesis and metastasis. ..
  32. Dinkelmann M, Spehalski E, Stoneham T, Buis J, Wu Y, Sekiguchi J, et al. Multiple functions of MRN in end-joining pathways during isotype class switching. Nat Struct Mol Biol. 2009;16:808-13 pubmed publisher
    The Mre11-Rad50-NBS1 (MRN) complex has many roles in response to DNA double-strand breaks, but its functions in repair by nonhomologous end joining (NHEJ) pathways are poorly understood...
  33. Pellegrini M, Claps G, Orlova V, Barrios F, Dolci S, Geremia R, et al. Targeted JAM-C deletion in germ cells by Spo11-controlled Cre recombinase. J Cell Sci. 2011;124:91-9 pubmed publisher
    ..Spo11(Cre) mice were then crossed with floxed Nbs1 and JAM-C mice to produce conditional knockouts...
  34. Liu B, Chen X. The distinct signaling regulatory roles in the cortical atrophy and cerebellar apoptosis of newborn Nbn-deficient mice. Cell Mol Neurobiol. 2013;33:1043-53 pubmed publisher
    Human Nijmegen breakage syndrome, caused by the hypomorphic mutation of Nbn gene, is a hereditary instability disease, characterized by chromosomal instability, immunodeficiency, radiosensitivity, cancer predisposition and microcephaly...
  35. Douglas K, Camper S. Partial transcriptome of the developing pituitary gland. Genomics. 2000;70:335-46 pubmed
    ..The tissue distribution, cell specificity, and developmental regulation were determined for a subset of the transcripts. ..
  36. Pacheco S, Marcet Ortega M, Lange J, Jasin M, Keeney S, Roig I. The ATM signaling cascade promotes recombination-dependent pachytene arrest in mouse spermatocytes. PLoS Genet. 2015;11:e1005017 pubmed publisher
    ..also progress to an H1t-positive stage if ATM activity is attenuated by hypomorphic mutations in Mre11 or Nbs1 or by elimination of the ATM-effector kinase CHK2...
  37. Seidel P, Remus M, Delacher M, Grigaravicius P, Reuss D, Frappart L, et al. Epidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis. Oncotarget. 2016;7:23006-18 pubmed publisher
    Nijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report a novel function of Nbn in skin homeostasis...
  38. Spehalski E, Capper K, Smith C, Morgan M, Dinkelmann M, Buis J, et al. MRE11 Promotes Tumorigenesis by Facilitating Resistance to Oncogene-Induced Replication Stress. Cancer Res. 2017;77:5327-5338 pubmed publisher
    Hypomorphic mutations in the genes encoding the MRE11/RAD50/NBS1 (MRN) DNA repair complex lead to cancer-prone syndromes...
  39. Yuan J, Chen J. MRE11-RAD50-NBS1 complex dictates DNA repair independent of H2AX. J Biol Chem. 2010;285:1097-104 pubmed publisher
    ..We demonstrate that the MRE11-RAD50-NBS1 (MRN) complex acts to promote DNA end resection and the generation of single-stranded DNA, which is critically ..
  40. Rodrigues P, Grigaravicius P, Remus M, Cavalheiro G, Gomes A, Rocha Martins M, et al. Nbn and atm cooperate in a tissue and developmental stage-specific manner to prevent double strand breaks and apoptosis in developing brain and eye. PLoS ONE. 2013;8:e69209 pubmed publisher
    b>Nibrin (NBN or NBS1) and ATM are key factors for DNA Double Strand Break (DSB) signaling and repair. Mutations in NBN or ATM result in Nijmegen Breakage Syndrome and Ataxia telangiectasia...
  41. Bruhn C, Zhou Z, Ai H, Wang Z. The essential function of the MRN complex in the resolution of endogenous replication intermediates. Cell Rep. 2014;6:182-95 pubmed publisher
    The MRN complex (Mre11/Rad50/Nbs1) is important in double-strand break (DSB) recognition, end resection, replication fork stabilization, and ATM and ATR activation...
  42. Katyal S, Lee Y, Nitiss K, Downing S, Li Y, Shimada M, et al. Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes. Nat Neurosci. 2014;17:813-21 pubmed publisher
    ..Our results identify a critical endogenous pathogenic lesion associated with neurodegenerative syndromes arising from DNA repair deficiency, indicating that genome integrity is important for preventing disease in the nervous system. ..
  43. Foster S, De S, Johnson L, Petrini J, Stracker T. Cell cycle- and DNA repair pathway-specific effects of apoptosis on tumor suppression. Proc Natl Acad Sci U S A. 2012;109:9953-8 pubmed publisher
    ..Previously, we have shown that the Chk2 kinase functions independently of the Mre11 complex (Mre11, Rad50, and Nbs1) and ATM in apoptosis and suppresses tumorigenesis resulting from hypomorphic alleles of Mre11 or Nbs1...
  44. Reynolds G, Gao Q, Miller D, Snow B, Harrington L, Murnane J. PIF1 disruption or NBS1 hypomorphism does not affect chromosome healing or fusion resulting from double-strand breaks near telomeres in murine embryonic stem cells. DNA Repair (Amst). 2011;10:1164-73 pubmed publisher
    ..Here, we employed a method of inducing DSBs near telomeres to query the role of two proteins, PIF1 and NBS1, in chromosome healing in mammalian cells...
  45. Yanagihara H, Kobayashi J, Tateishi S, Kato A, Matsuura S, Tauchi H, et al. NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol ?-dependent translesion DNA synthesis. Mol Cell. 2011;43:788-97 pubmed publisher
    ..We show that NBS1 (mutated in Nijmegen breakage syndrome) binds to RAD18 after UV irradiation and mediates the recruitment of RAD18 ..
  46. Li T, Wang Z. Point mutation at the Nbs1 Threonine 278 site does not affect mouse development, but compromises the Chk2 and Smc1 phosphorylation after DNA damage. Mech Ageing Dev. 2011;132:382-8 pubmed publisher
    b>NBS1, mutated in Nijmegen breakage syndrome (NBS), senses the DNA double strand breaks (DSBs) and initiates the DNA damage response (DDR) by activating ATM kinase...
  47. Liu B, Chen X, Wang Z, Tong W. Nbn gene inactivation in the CNS of mouse inhibits the myelinating ability of the mature cortical oligodendrocytes. Glia. 2014;62:133-44 pubmed publisher
    ..molecular mechanisms of the NBS microcephaly are still obscure, thus our group previously inactivated the Nbn gene in the central nervous system (CNS) of mice by nestin-Cre targeting gene system, and generated Nbn(CNS-del) ..
  48. Pereira Lopes S, Tur J, Calatayud Subias J, Lloberas J, Stracker T, Celada A. NBS1 is required for macrophage homeostasis and functional activity in mice. Blood. 2015;126:2502-10 pubmed publisher
    Nijmegen breakage syndrome 1 (NBS1) is a component of the MRE11 complex, which is a sensor of DNA double-strand breaks and plays a crucial role in the DNA damage response...
  49. Vissinga C, Yeo T, Warren S, Brawley J, Phillips J, Cerosaletti K, et al. Nuclear export of NBN is required for normal cellular responses to radiation. Mol Cell Biol. 2009;29:1000-6 pubmed publisher
    Nijmegen breakage syndrome arises from hypomorphic mutations in the NBN gene encoding nibrin, a component of the MRE11/RAD50/nibrin (MRN) complex...
  50. Weiss R, Leder P, Vaziri C. Critical role for mouse Hus1 in an S-phase DNA damage cell cycle checkpoint. Mol Cell Biol. 2003;23:791-803 pubmed
    ..Conversely, checkpoint-mediated inhibition of DNA synthesis in response to BPDE did not require NBS1, a component of the IR-responsive S-phase checkpoint pathway...
  51. Dimitrova N, de Lange T. Cell cycle-dependent role of MRN at dysfunctional telomeres: ATM signaling-dependent induction of nonhomologous end joining (NHEJ) in G1 and resection-mediated inhibition of NHEJ in G2. Mol Cell Biol. 2009;29:5552-63 pubmed publisher
    Here, we address the role of the MRN (Mre11/Rad50/Nbs1) complex in the response to telomeres rendered dysfunctional by deletion of the shelterin component TRF2...
  52. Stracker T, Williams B, Deriano L, Theunissen J, Adelman C, Roth D, et al. Artemis and nonhomologous end joining-independent influence of DNA-dependent protein kinase catalytic subunit on chromosome stability. Mol Cell Biol. 2009;29:503-14 pubmed publisher
    ..In contrast, the more moderate DNA double-strand break response defects associated with the Nbs1(DeltaB) allele permitted viability of some Nbs1(DeltaB/DeltaB) Prkdc(scid/scid) embryos...
  53. Wessendorf P, Vijg J, Nussenzweig A, Digweed M. Deficiency of the DNA repair protein nibrin increases the basal but not the radiation induced mutation frequency in vivo. Mutat Res. 2014;769:11-6 pubmed publisher
    b>Nibrin (NBN) is a member of a DNA repair complex together with MRE11 and RAD50. The complex is associated particularly with the repair of DNA double strand breaks and with the regulation of cell cycle check points...
  54. Yuan Z, Seto E. A functional link between SIRT1 deacetylase and NBS1 in DNA damage response. Cell Cycle. 2007;6:2869-71 pubmed
    ..phosphorylated by ATM in response to DSBs, and the sequential phosphorylation of some of these factors, including NBS1, delay cell cycle progression (checkpoint arrest) to allow time for DNA damage repair...
  55. Reimann M, Loddenkemper C, Rudolph C, Schildhauer I, Teichmann B, Stein H, et al. The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo. Blood. 2007;110:2996-3004 pubmed
    ..Hence, Atm eliminates preneoplastic lesions by converting oncogenic signaling into apoptosis, and selection against an Atm-dependent response promotes formation of lymphomas with predetermined treatment insensitivity. ..
  56. Morales M, Theunissen J, Kim C, Kitagawa R, Kastan M, Petrini J. The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 2005;19:3043-54 pubmed
    ..data from Saccharomyces cerevisiae and mammals implicate the Mre11 complex, consisting of Mre11, Rad50, and Nbs1, as a sensor of DNA damage, and indicate that the complex influences the activity of ataxia-telangiectasia mutated (..
  57. Kumar A, Fernandez Capetillo O, Fernadez Capetillo O, Carrera A. Nuclear phosphoinositide 3-kinase beta controls double-strand break DNA repair. Proc Natl Acad Sci U S A. 2010;107:7491-6 pubmed publisher
    ..We show that PI3Kbeta is necessary for DSB sensing, as PI3Kbeta regulates binding of the Nbs1 sensor protein to damaged DNA...
  58. Melchers A, Stockl L, Radszewski J, Anders M, Krenzlin H, Kalischke C, et al. A systematic proteomic study of irradiated DNA repair deficient Nbn-mice. PLoS ONE. 2009;4:e5423 pubmed publisher
    The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs). The NBN gene is essential in mammals...
  59. Vissinga C, Yeo T, Woessner J, Massa H, Wilson R, Trask B, et al. Identification, characterization, and mapping of a mouse homolog of the gene mutated in Nijmegen breakage syndrome. Cytogenet Cell Genet. 1999;87:80-4 pubmed
    The rare autosomal recessive disorder Nijmegen breakage syndrome (NBS) results from mutations in the NBS1 gene on human chromosome 8q21. A mouse homolog of the NBS1 gene was isolated and its nucleotide sequence determined...
  60. Begum N, Kinoshita K, Kakazu N, Muramatsu M, Nagaoka H, Shinkura R, et al. Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch. Science. 2004;305:1160-3 pubmed
    ..These results indicate that UNG is involved in the repair step of CSR yet by an unknown mechanism. The dispensability of U removal in the DNA cleavage step of CSR requires a reconsideration of the model of DNA deamination by AID. ..
  61. Lombard D, Guarente L. Nijmegen breakage syndrome disease protein and MRE11 at PML nuclear bodies and meiotic telomeres. Cancer Res. 2000;60:2331-4 pubmed
    ..These results implicate the NBs in the maintenance of genomic stability and suggest that p95 and MRE11 may have roles in telomere maintenance in mammals, analogous to the role their homologues play in yeast. ..
  62. Daniel J, Pellegrini M, Lee B, Guo Z, Filsuf D, Belkina N, et al. Loss of ATM kinase activity leads to embryonic lethality in mice. J Cell Biol. 2012;198:295-304 pubmed publisher
    ..We propose that ATM kinase-inactive missense mutations, unless otherwise compensated for, interfere with HR during embryogenesis. ..
  63. Brugmans L, Verkaik N, Kunen M, van Drunen E, Williams B, Petrini J, et al. NBS1 cooperates with homologous recombination to counteract chromosome breakage during replication. DNA Repair (Amst). 2009;8:1363-70 pubmed publisher
    ..NBS patients contain a mutation in the NBS1 gene, which encodes the NBS1 component of the DNA double-strand break (DSB) response complex MRE11/RAD50/NBS1...
  64. Mahmoudi M, Gorenne I, Mercer J, Figg N, Littlewood T, Bennett M. Statins use a novel Nijmegen breakage syndrome-1-dependent pathway to accelerate DNA repair in vascular smooth muscle cells. Circ Res. 2008;103:717-25 pubmed publisher
    ..We conclude that statins activate a novel mechanism of accelerating DNA repair, dependent on NBS-1 stabilization and Hdm2. Statin treatment may delay cell senescence and promote DNA repair in atherosclerosis. ..