{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:57:02Z","timestamp":1792058222553,"version":"4.4.0"},"reference-count":52,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,8,19]]},"abstract":"<jats:p>Nonreciprocal translocations and gene amplifications are commonly found in human tumors. Although little is known about the mechanisms leading to such aberrations, tissue culture models predict that they can arise from DNA breakage, followed by cycles of chromatid fusion, asymmetric mitotic breakage, and replication. Mice deficient in both a nonhomologous end joining (NHEJ) DNA repair protein and the p53 tumor suppressor develop lymphomas at an early age harboring amplification of an IgH\/c-myc fusion. Here we report that these chromosomal rearrangements are initiated by a recombination activating gene (RAG)-induced DNA cleavage. Subsequent DNA repair events juxtaposing IgH and c-myc are mediated by a break-induced replication pathway. Cycles of breakage-fusion-bridge result in amplification of IgH\/c-myc while chromosome stabilization occurs through telomere capture. Thus, mice deficient in NHEJ provide excellent models to study the etiology of unbalanced translocations and amplification events during tumorigenesis.<\/jats:p>","DOI":"10.1084\/jem.20020851","type":"journal-article","created":{"date-parts":[[2002,9,30]],"date-time":"2002-09-30T17:03:17Z","timestamp":1033405397000},"page":"469-480","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":194,"title":["Evidence for Replicative Repair of DNA Double-Strand Breaks Leading to Oncogenic Translocation and Gene Amplification"],"prefix":"10.1084","volume":"196","author":[{"given":"Michael J.","family":"Difilippantonio","sequence":"first","affiliation":[{"name":"1Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Petersen","sequence":"additional","affiliation":[{"name":"2Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua Tang","family":"Chen","sequence":"additional","affiliation":[{"name":"2Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Johnson","sequence":"additional","affiliation":[{"name":"3Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Jasin","sequence":"additional","affiliation":[{"name":"3Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Kanaar","sequence":"additional","affiliation":[{"name":"4Department of Cell Biology and Genetics, Erasmus University Rotterdam, 3000 DR Rotterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ried","sequence":"additional","affiliation":[{"name":"1Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre\u0301","family":"Nussenzweig","sequence":"additional","affiliation":[{"name":"2Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2002,8,19]]},"reference":[{"key":"2023072511454439500_BIB1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/35015097","volume":"405","year":"2000","journal-title":"Nature."},{"key":"2023072511454439500_BIB2","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/emboj\/17.1.325","volume":"17","year":"1998","journal-title":"EMBO J."},{"key":"2023072511454439500_BIB3","first-page":"S45","volume":"109(Suppl.)","year":"2002","journal-title":"Cell."},{"key":"2023072511454439500_BIB4","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/35006670","volume":"404","year":"2000","journal-title":"Nature."},{"key":"2023072511454439500_BIB5","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/S0960-9822(00)80123-2","volume":"9","year":"1999","journal-title":"Curr. Biol."},{"key":"2023072511454439500_BIB6","doi-asserted-by":"crossref","first-page":"6630","DOI":"10.1073\/pnas.110152897","volume":"97","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511454439500_BIB7","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/S1097-2765(00)80264-6","volume":"5","year":"2000","journal-title":"Mol. Cell."},{"key":"2023072511454439500_BIB8","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/35009138","volume":"404","year":"2000","journal-title":"Nature."},{"key":"2023072511454439500_BIB9","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1101\/gad.10.16.2038","volume":"10","year":"1996","journal-title":"Genes Dev."},{"key":"2023072511454439500_BIB10","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1128\/MCB.20.11.3772-3780.2000","volume":"20","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2023072511454439500_BIB11","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1101\/gad.10.16.2055","volume":"10","year":"1996","journal-title":"Genes Dev."},{"key":"2023072511454439500_BIB12","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1172\/JCI6658","volume":"103","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2023072511454439500_BIB13","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/S1097-2765(01)00425-7","volume":"8","year":"2001","journal-title":"Mol. Cell."},{"key":"2023072511454439500_BIB14","doi-asserted-by":"crossref","first-page":"6347","DOI":"10.4049\/jimmunol.165.11.6347","volume":"165","year":"2000","journal-title":"J. Immunol."},{"key":"2023072511454439500_BIB15","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0960-9822(99)80311-X","volume":"9","year":"1999","journal-title":"Curr. Biol."},{"key":"2023072511454439500_BIB16","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S1097-2765(01)00408-7","volume":"8","year":"2001","journal-title":"Mol. Cell."},{"key":"2023072511454439500_BIB17","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1074-7613(00)80386-6","volume":"7","year":"1997","journal-title":"Immunity"},{"key":"2023072511454439500_BIB18"},{"key":"2023072511454439500_BIB19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/356215a0","volume":"356","year":"1992","journal-title":"Nature."},{"key":"2023072511454439500_BIB20","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/362847a0","volume":"362","year":"1993","journal-title":"Nature."},{"key":"2023072511454439500_BIB21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0092-8674(00)80199-3","volume":"89","year":"1997","journal-title":"Cell."},{"key":"2023072511454439500_BIB22","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1182\/blood.V96.5.1940","volume":"96","year":"2000","journal-title":"Blood."},{"key":"2023072511454439500_BIB23","doi-asserted-by":"crossref","first-page":"6978","DOI":"10.1073\/pnas.89.15.6978","volume":"89","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511454439500_BIB24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0092-8674(00)80086-0","volume":"86","year":"1996","journal-title":"Cell."},{"key":"2023072511454439500_BIB25","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/ng1297-483","volume":"17","year":"1997","journal-title":"Nat. Genet."},{"key":"2023072511454439500_BIB26","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/ng1297-479","volume":"17","year":"1997","journal-title":"Nat. Genet."},{"key":"2023072511454439500_BIB27","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1084\/jem.186.6.921","volume":"186","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072511454439500_BIB28","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1128\/MCB.20.9.3147-3156.2000","volume":"20","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2023072511454439500_BIB29","doi-asserted-by":"crossref","first-page":"7837","DOI":"10.1073\/pnas.79.24.7837","volume":"79","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511454439500_BIB30","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0304-3835(01)00472-4","volume":"167","year":"2001","journal-title":"Cancer Lett."},{"key":"2023072511454439500_BIB31","doi-asserted-by":"crossref","first-page":"5611","DOI":"10.1038\/sj.onc.1204641","volume":"20","year":"2001","journal-title":"Oncogene."},{"key":"2023072511454439500_BIB32","doi-asserted-by":"crossref","first-page":"8929","DOI":"10.1073\/pnas.93.17.8929","volume":"93","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511454439500_BIB33","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1126\/science.8469973","volume":"260","year":"1993","journal-title":"Science."},{"key":"2023072511454439500_BIB34","doi-asserted-by":"crossref","first-page":"5333","DOI":"10.1093\/nar\/26.23.5333","volume":"26","year":"1998","journal-title":"Nucleic Acids Res."},{"key":"2023072511454439500_BIB35","doi-asserted-by":"crossref","first-page":"6664","DOI":"10.1073\/pnas.97.12.6664","volume":"97","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511454439500_BIB36","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1128\/MCB.18.6.3495","volume":"18","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"2023072511454439500_BIB37","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/29457","volume":"394","year":"1998","journal-title":"Nature."},{"key":"2023072511454439500_BIB38","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0092-8674(00)81587-1","volume":"94","year":"1998","journal-title":"Cell."},{"key":"2023072511454439500_BIB39","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1128\/MCB.22.7.2068-2077.2002","volume":"22","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"2023072511454439500_BIB40","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2484::AID-IMMU2484>3.0.CO;2-B","volume":"29","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2023072511454439500_BIB41","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/genetics\/150.3.1037","volume":"150","year":"1998","journal-title":"Genetics."},{"key":"2023072511454439500_BIB42","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/genetics\/147.2.371","volume":"147","year":"1997","journal-title":"Genetics."},{"key":"2023072511454439500_BIB43","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1128\/MCB.21.6.2048-2056.2001","volume":"21","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"2023072511454439500_BIB44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1098\/rstb.1995.0008","volume":"347","year":"1995","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"2023072511454439500_BIB45","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0092-8674(00)80201-9","volume":"89","year":"1997","journal-title":"Cell."},{"key":"2023072511454439500_BIB46"},{"key":"2023072511454439500_BIB47","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/0092-8674(92)90243-6","volume":"70","year":"1992","journal-title":"Cell."},{"key":"2023072511454439500_BIB48","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/0092-8674(92)90244-7","volume":"70","year":"1992","journal-title":"Cell."},{"key":"2023072511454439500_BIB49","first-page":"1453","volume":"6","year":"1991","journal-title":"Oncogene."},{"key":"2023072511454439500_BIB50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1101\/SQB.1951.016.01.004","volume":"16","year":"1951","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"2023072511454439500_BIB51","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/ng0793-252","volume":"4","year":"1993","journal-title":"Nat. Genet."},{"key":"2023072511454439500_BIB52","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1038\/sj.onc.1205244","volume":"21","year":"2002","journal-title":"Oncogene."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/196\/4\/469\/1708092\/jem1964469.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/196\/4\/469\/1708092\/jem1964469.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T11:46:33Z","timestamp":1690285593000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/196\/4\/469\/8412\/Evidence-for-Replicative-Repair-of-DNA-Double"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,8,19]]},"references-count":52,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2002,8,19]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20020851","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2002,8,19]]}}}