{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:53:42Z","timestamp":1790805222039,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2002,3,15]],"date-time":"2002-03-15T00:00:00Z","timestamp":1016150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2002,3,15]],"date-time":"2002-03-15T00:00:00Z","timestamp":1016150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"published-print":{"date-parts":[[2002,3,15]]},"DOI":"10.1093\/emboj\/21.6.1447","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T18:42:52Z","timestamp":1027708972000},"page":"1447-1455","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Targeted disruption of NBS1 reveals its roles in mouse development and DNA repair"],"prefix":"10.1038","volume":"21","author":[{"given":"Jian","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick T.","family":"Bronson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2002,3,15]]},"reference":[{"key":"BFEMBJ7594363_CR1","first-page":"5934","volume":"60","author":"JY Ahn","year":"2000","unstructured":"Ahn JY, Schwarz JK, Piwnica\u2010Worms H and Canman CE (2000) Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res, 60, 5934\u20135936.","journal-title":"Cancer Res"},{"key":"BFEMBJ7594363_CR2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0092-8674(00)80086-0","volume":"86","author":"C Barlow","year":"1996","unstructured":"Barlow C et al. (1996) Atm\u2010deficient mice: a paradigm of ataxia telangiectasia. Cell, 86, 159\u2013171.","journal-title":"Cell"},{"key":"BFEMBJ7594363_CR3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/09553009414550211","volume":"65","author":"H Beamish","year":"1994","unstructured":"Beamish H and Lavin MF (1994) Radiosensitivity in ataxia\u2010telangiectasia: anomalies in radiation\u2010induced cell cycle delay. Int J Radiat Biol, 65, 175\u2013184.","journal-title":"Int J Radiat Biol"},{"key":"BFEMBJ7594363_CR4","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1128\/MCB.21.15.5214-5222.2001","volume":"21","author":"G Buscemi","year":"2001","unstructured":"Buscemi G et al. (2001) Chk2 activation dependence on Nbs1 after DNA damage. Mol Cell Biol, 21, 5214\u20135222.","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ7594363_CR5","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0092-8674(00)81175-7","volume":"93","author":"JP Carney","year":"1998","unstructured":"Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR,III, Hays L, Morgan WF and Petrini JH (1998) The hMre11\/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double\u2010strand break repair to the cellular DNA damage response. Cell, 93, 477\u2013486.","journal-title":"Cell"},{"key":"BFEMBJ7594363_CR6","doi-asserted-by":"crossref","first-page":"345","DOI":"10.4049\/jimmunol.164.1.345","volume":"164","author":"C Chao","year":"2000","unstructured":"Chao C, Yang EM and Xu Y (2000) Rescue of defective T cell development and function in Atm\u2212\/\u2212 mice by a functional TCR \u03b1\u03b2 transgene. J Immunol, 164, 345\u2013349.","journal-title":"J Immunol"},{"key":"BFEMBJ7594363_CR7","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1126\/science.290.5498.1962","volume":"290","author":"HT Chen","year":"2000","unstructured":"Chen HT et al. (2000) Response to RAG\u2010mediated VDJ cleavage by NBS1 and \u03b3\u2010H2AX. Science, 290, 1962\u20131965.","journal-title":"Science"},{"key":"BFEMBJ7594363_CR8","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1126\/science.286.5442.1162","volume":"286","author":"D Cortez","year":"1999","unstructured":"Cortez D, Wang Y, Qin J and Elledge SJ (1999) Requirement of ATM\u2010dependent phosphorylation of brca1 in the DNA damage response to double\u2010strand breaks. Science, 286, 1162\u20131166.","journal-title":"Science"},{"key":"BFEMBJ7594363_CR9","doi-asserted-by":"crossref","first-page":"7883","DOI":"10.1038\/sj.onc.1203283","volume":"18","author":"GK Dasika","year":"1999","unstructured":"Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A and Lee EY (1999) DNA damage\u2010induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene, 18, 7883\u20137899.","journal-title":"Oncogene"},{"key":"BFEMBJ7594363_CR10","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1128\/MCB.21.6.2184-2191.2001","volume":"21","author":"A Desai\u2010Mehta","year":"2001","unstructured":"Desai\u2010Mehta A, Cerosaletti KM and Concannon P (2001) Distinct functional domains of nibrin mediate Mre11 binding, focus formation and nuclear localization. Mol Cell Biol, 21, 2184\u20132191.","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ7594363_CR11","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0952-7915(00)00256-9","volume":"13","author":"A Durandy","year":"2001","unstructured":"Durandy A and Honjo T (2001) Human genetic defects in class\u2010switch recombination (hyper\u2010IgM syndromes). Curr Opin Immunol, 13, 543\u2013548.","journal-title":"Curr Opin Immunol"},{"key":"BFEMBJ7594363_CR12","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev.immunol.17.1.523","volume":"17","author":"W Ellmeier","year":"1999","unstructured":"Ellmeier W, Sawada S and Littman DR (1999) The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu Rev Immunol, 17, 523\u2013554.","journal-title":"Annu Rev Immunol"},{"key":"BFEMBJ7594363_CR13","doi-asserted-by":"crossref","first-page":"13084","DOI":"10.1073\/pnas.93.23.13084","volume":"93","author":"A Elson","year":"1996","unstructured":"Elson A, Wang Y, Daugherty CJ, Morton CC, Zhou F, Campos\u2010Torres J and Leder P (1996) Pleiotropic defects in ataxia\u2010telangiectasia protein\u2010deficient mice. Proc Natl Acad Sci USA, 93, 13084\u201313089.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ7594363_CR14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/75508","volume":"25","author":"M Gatei","year":"2000","unstructured":"Gatei M et al. (2000) ATM\u2010dependent phosphorylation of nibrin in response to radiation exposure. Nature Genet, 25, 115\u2013119.","journal-title":"Nature Genet"},{"key":"BFEMBJ7594363_CR15","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1146\/annurev.immunol.19.1.595","volume":"19","author":"RR Hardy","year":"2001","unstructured":"Hardy RR and Hayakawa K (2001) B cell development pathways. Annu Rev Immunol, 19, 595\u2013621.","journal-title":"Annu Rev Immunol"},{"key":"BFEMBJ7594363_CR16","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1126\/science.287.5459.1824","volume":"287","author":"A Hirao","year":"2000","unstructured":"Hirao A, Kong YY, Matsuoka S, Wakeham A, Ruland J, Yoshida H, Liu D, Elledge SJ and Mak TW (2000) DNA damage\u2010induced activation of p53 by the checkpoint kinase Chk2. Science, 287, 1824\u20131827.","journal-title":"Science"},{"key":"BFEMBJ7594363_CR17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2307\/3578563","volume":"140","author":"JH Hong","year":"1994","unstructured":"Hong JH, Gatti RA, Huo YK, Chiang CS and McBride WH (1994) G2\/M\u2010phase arrest and release in ataxia telangiectasia and normal cells after exposure to ionizing radiation. Radiat Res, 140, 17\u201323.","journal-title":"Radiat Res"},{"key":"BFEMBJ7594363_CR18","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1006\/bbrc.1999.1737","volume":"265","author":"A Ito","year":"1999","unstructured":"Ito A, Tauchi H, Kobayashi J, Morishima K, Nakamura A, Hirokawa Y, Matsuura S, Ito K and Komatsu K (1999) Expression of full\u2010length NBS1 protein restores normal radiation responses in cells from Nijmegen breakage syndrome patients. Biochem Biophys Res Commun, 265, 716\u2013721.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFEMBJ7594363_CR19","first-page":"187","volume":"58","author":"P Kisielow","year":"1995","unstructured":"Kisielow P and von Boehmer H (1995) Development and selection of T cells: facts and puzzles. Adv Immunol, 58, 187\u2013209.","journal-title":"Adv Immunol"},{"key":"BFEMBJ7594363_CR20","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0165-4608(91)90164-P","volume":"56","author":"TL Kojis","year":"1991","unstructured":"Kojis TL, Gatti RA and Sparkes RS (1991) The cytogenetics of ataxia telangiectasia. Cancer Genet Cytogenet, 56, 143\u2013156.","journal-title":"Cancer Genet Cytogenet"},{"key":"BFEMBJ7594363_CR21","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/35018134","volume":"406","author":"S Li","year":"2000","unstructured":"Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY and Lee WH (2000) Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature, 406, 210\u2013215.","journal-title":"Nature"},{"key":"BFEMBJ7594363_CR22","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/35007091","volume":"404","author":"DS Lim","year":"2000","unstructured":"Lim DS, Kim ST, Xu B, Maser RS, Lin J, Petrini JH and Kastan MB (2000) ATM phosphorylates p95\/nbs1 in an S\u2010phase checkpoint pathway. Nature, 404, 613\u2013617.","journal-title":"Nature"},{"key":"BFEMBJ7594363_CR23","first-page":"4408","volume":"57","author":"F Lista","year":"1997","unstructured":"Lista F, Bertness V, Guidos CJ, Danska JS and Kirsch IR (1997) The absolute number of trans\u2010rearrangements between the TCRG and TCRB loci is predictive of lymphoma risk: a severe combined immune deficiency (SCID) murine model. Cancer Res, 57, 4408\u20134413.","journal-title":"Cancer Res"},{"key":"BFEMBJ7594363_CR24","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/86920","volume":"27","author":"RS Maser","year":"2001","unstructured":"Maser RS, Zinkel R and Petrini JH (2001) An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele. Nature Genet, 27, 417\u2013421.","journal-title":"Nature Genet"},{"key":"BFEMBJ7594363_CR25","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1126\/science.282.5395.1893","volume":"282","author":"S Matsuoka","year":"1998","unstructured":"Matsuoka S, Huang M and Elledge SJ (1998) Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science, 282, 1893\u20131897.","journal-title":"Science"},{"key":"BFEMBJ7594363_CR26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/549","volume":"19","author":"S Matsuura","year":"1998","unstructured":"Matsuura S et al. (1998) Positional cloning of the gene for Nijmegen breakage syndrome. Nature Genet, 19, 179\u2013181.","journal-title":"Nature Genet"},{"key":"BFEMBJ7594363_CR27","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/35036406","volume":"2","author":"R Melchionna","year":"2000","unstructured":"Melchionna R, Chen XB, Blasina A and McGowan CH (2000) Threonine 68 is required for radiation\u2010induced phosphorylation and activation of Cds1. Nature Cell Biol, 2, 762\u2013765.","journal-title":"Nature Cell Biol"},{"key":"BFEMBJ7594363_CR28","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S1097-2765(00)80202-6","volume":"4","author":"ME Moynahan","year":"1999","unstructured":"Moynahan ME, Chiu JW, Koller BH and Jasin M (1999) Brca1 controls homology\u2010directed DNA repair. Mol Cell, 4, 511\u2013518.","journal-title":"Mol Cell"},{"key":"BFEMBJ7594363_CR29","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1101\/gad.13.10.1276","volume":"13","author":"TT Paull","year":"1999","unstructured":"Paull TT and Gellert M (1999) Nbs1 potentiates ATP\u2010driven DNA unwinding and endonuclease cleavage by the Mre11\/Rad50 complex. Genes Dev, 13, 1276\u20131288.","journal-title":"Genes Dev"},{"key":"BFEMBJ7594363_CR30","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/S0955-0674(00)00278-7","volume":"13","author":"M Serrano","year":"2001","unstructured":"Serrano M and Blasco MA (2001) Putting the stress on senescence. Curr Opin Cell Biol, 13, 748\u2013753.","journal-title":"Curr Opin Cell Biol"},{"key":"BFEMBJ7594363_CR31","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1146\/annurev.immunol.14.1.459","volume":"14","author":"BP Sleckman","year":"1996","unstructured":"Sleckman BP, Gorman JR and Alt FW (1996) Accessibility control of antigen\u2010receptor variable\u2010region gene assembly: role of cis\u2010acting elements. Annu Rev Immunol, 14, 459\u2013481.","journal-title":"Annu Rev Immunol"},{"key":"BFEMBJ7594363_CR32","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(00)81547-0","volume":"99","author":"GS Stewart","year":"1999","unstructured":"Stewart GS et al. (1999) The DNA double\u2010strand break repair gene hMRE11 is mutated in individuals with an ataxia\u2010telangiectasia\u2010like disorder. Cell, 99, 577\u2013587.","journal-title":"Cell"},{"key":"BFEMBJ7594363_CR33","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000056900","volume":"92","author":"M Stumm","year":"2001","unstructured":"Stumm M, Neubauer S, Keindorff S, Wegner RD, Wieacker P and Sauer R (2001) High frequency of spontaneous translocations revealed by FISH in cells from patients with the cancer\u2010prone syndromes ataxia telangiectasia and Nijmegen breakage syndrome. Cytogenet Cell Genet, 92, 186\u2013191.","journal-title":"Cytogenet Cell Genet"},{"key":"BFEMBJ7594363_CR34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1006\/clin.1996.4275","volume":"82","author":"KE Sullivan","year":"1997","unstructured":"Sullivan KE, Veksler E, Lederman H and Lees\u2010Miller SP (1997) Cell cycle checkpoints and DNA repair in Nijmegen breakage syndrome. Clin Immunol Immunopathol, 82, 43\u201348.","journal-title":"Clin Immunol Immunopathol"},{"key":"BFEMBJ7594363_CR35","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1136\/jmg.33.2.153","volume":"33","author":"I van der Burgt","year":"1996","unstructured":"van der Burgt I, Chrzanowska KH, Smeets D and Weemaes C (1996) Nijmegen breakage syndrome. J Med Genet, 33, 153\u2013156.","journal-title":"J Med Genet"},{"key":"BFEMBJ7594363_CR36","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0092-8674(00)81174-5","volume":"93","author":"R Varon","year":"1998","unstructured":"Varon R et al. (1998) Nibrin, a novel DNA double\u2010strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell, 93, 467\u2013476.","journal-title":"Cell"},{"key":"BFEMBJ7594363_CR37","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/41225","volume":"388","author":"DT Weaver","year":"1997","unstructured":"Weaver DT and Alt FW (1997) V(D)J recombination. From RAGs to stitches. Nature, 388, 428\u2013429.","journal-title":"Nature"},{"key":"BFEMBJ7594363_CR38","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/35013089","volume":"405","author":"X Wu","year":"2000","unstructured":"Wu X et al. (2000) ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Nature, 405, 477\u2013482.","journal-title":"Nature"},{"key":"BFEMBJ7594363_CR40","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1101\/gad.10.19.2401","volume":"10","author":"Y Xu","year":"1996","unstructured":"Xu Y and Baltimore D (1996) Dual roles of ATM in the cellular response to radiation and in cell growth control. Genes Dev, 10, 2401\u20132410.","journal-title":"Genes Dev"},{"key":"BFEMBJ7594363_CR39","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1101\/gad.10.19.2411","volume":"10","author":"Y Xu","year":"1996","unstructured":"Xu Y, Ashley T, Brainerd EE, Bronson RT, Meyn MS and Baltimore D (1996) Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects and thymic lymphoma. Genes Dev, 10, 2411\u20132422.","journal-title":"Genes Dev"},{"key":"BFEMBJ7594363_CR41","doi-asserted-by":"crossref","first-page":"4385","DOI":"10.1128\/MCB.18.7.4385","volume":"18","author":"Y Xu","year":"1998","unstructured":"Xu Y, Yang EM, Brugarolas J, Jacks T and Baltimore D (1998) Involvement of p53 and p21 in cellular defects and tumorigenesis in atm\u2212\/\u2212 mice. Mol Cell Biol, 18, 4385\u20134390.","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ7594363_CR42","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/35013083","volume":"405","author":"S Zhao","year":"2000","unstructured":"Zhao S et al. (2000) Functional link between ataxia\u2010telangiectasia and Nijmegen breakage syndrome gene products. Nature, 405, 473\u2013477.","journal-title":"Nature"},{"key":"BFEMBJ7594363_CR43","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0960-9822(01)00019-7","volume":"11","author":"J Zhu","year":"2001","unstructured":"Zhu J, Petersen S, Tessarollo L and Nussenzweig A (2001) Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice. Curr Biol, 11, 105\u2013109.","journal-title":"Curr Biol"}],"container-title":["The EMBO Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1093%2Femboj%2F21.6.1447","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1093\/emboj\/21.6.1447.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1093\/emboj\/21.6.1447\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1093\/emboj\/21.6.1447","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1093\/emboj\/21.6.1447.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:03:57Z","timestamp":1779303837000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1093\/emboj\/21.6.1447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,3,15]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2002,3,15]]}},"alternative-id":["BFEMBJ7594363"],"URL":"https:\/\/doi.org\/10.1093\/emboj\/21.6.1447","relation":{},"ISSN":["0261-4189","1460-2075"],"issn-type":[{"value":"0261-4189","type":"print"},{"value":"1460-2075","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,3,15]]},"assertion":[{"value":"23 November 2001","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2002","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2002","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2002","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}