{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:00:18Z","timestamp":1762160418836},"reference-count":36,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,12,1]]},"abstract":"<jats:p>Previously we used the topoisomerase I inhibitor camptothecin (CPT), which kills mainly S-phase cells primarily by inducing double strand breaks (DSBs) in replication forks, to show that ataxia telangiectasia (A-T) fibroblasts are defective in the repair of this particular subclass of DSBs. CPT treated A-T cells reaching G2 have abnormally high levels of chromatid exchanges, viewed as prematurely condensed G2 chromosomes (G2 PCC), compared with normal cells where aberrations are mostly chromatid breaks. Here we show that A-T lymphoblastoid cells established from individuals with different mutations in the ATM gene also exhibit increased levels of chromosomal exchanges in response to CPT, indicating that the replication-associated DSBs are misrepaired in all these cells. From family studies we show that the presence of a single mutated allele in obligate A-T heterozygotes leads to intermediate levels of chromosomal exchanges in CPT-treated lymphoblastoid cells, thus providing a functional and sensitive assay to identify these individuals.<\/jats:p>","DOI":"10.1007\/s10540-005-2796-6","type":"journal-article","created":{"date-parts":[[2005,9,12]],"date-time":"2005-09-12T07:23:52Z","timestamp":1126509832000},"page":"617-629","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genome Instability in Ataxia Telangiectasia (A-T) Families: Camptothecin-Induced Damage to Replicating DNA Discriminates between Obligate A-T Heterozygotes, A-T Homozygotes and Controls"],"prefix":"10.1042","volume":"24","author":[{"given":"Jay C.","family":"Leonard","sequence":"first","affiliation":[{"name":"Coriell Cell Repositories, Coriell Institute for Medical Research, 403 Haddon Avenue, Camden, New Jersey, 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann M.","family":"Mullinger","sequence":"additional","affiliation":[{"name":"Coriell Cell Repositories, Coriell Institute for Medical Research, 403 Haddon Avenue, Camden, New Jersey, 08103, USA"},{"name":"Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Coriell Cell Repositories, Coriell Institute for Medical Research, 403 Haddon Avenue, Camden, New Jersey, 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather J.","family":"Cordell","sequence":"additional","affiliation":[{"name":"JDRF\/WT Diabetes and Inflammation Laboratory, Department of Medical Genetics, University of Cambridge, Cambridge, CB2 2XY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert T.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Coriell Cell Repositories, Coriell Institute for Medical Research, 403 Haddon Avenue, Camden, New Jersey, 08103, USA"},{"name":"Mary Lyon Centre, Medical Research Council, Harwell, Didcot, Oxfordshire, OX11 ORD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2005,9,12]]},"reference":[{"key":"2796_CR1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev.immunol.15.1.177","volume":"15","author":"M. F. Lavin","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"2796_CR2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1080\/09553009414551671","volume":"66","author":"J. Thacker","year":"1994","journal-title":"Int. J. Radiat. Biol."},{"key":"2796_CR3","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1093\/nar\/8.16.3709","volume":"8","author":"J. Houldsworth","year":"1980","journal-title":"Nucleic Acids Res."},{"key":"2796_CR4","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1073\/pnas.77.12.7315","volume":"77","author":"R. B. Painter","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2796_CR5","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1126\/science.7792600","volume":"268","author":"K. Savitsky","year":"1995","journal-title":"Science"},{"key":"2796_CR6","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrc1011","volume":"3","author":"Y. Shiloh","year":"2003","journal-title":"Natl. Rev. Cancer"},{"key":"2796_CR7","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1006\/bbrc.1999.1024","volume":"261","author":"R. T. Johnson","year":"1999","journal-title":"Biochem. Biophys. Res. Co."},{"key":"2796_CR8","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1093\/nar\/19.12.3295","volume":"19","author":"A. J. Ryan","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"2796_CR9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/09553008914550271","volume":"55","author":"P. J. Smith","year":"1989","journal-title":"Int. J. Radiat. Biol."},{"key":"2796_CR10","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/ajmg.1320420524","volume":"42","author":"L. Chessa","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"2796_CR11","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/hmg\/5.4.433","volume":"5","author":"S. Gilad","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"2796_CR12","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1086\/301755","volume":"62","author":"S. Gilad","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"2796_CR13","first-page":"839","volume":"59","author":"J. Wright","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"2796_CR14","first-page":"40","volume":"59","author":"M. Telatar","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"2796_CR15","unstructured":"Mitelman, F. S. (ed.) (1995) ISCN 1995 An International System for Human Cytogenetic Nomenclature. Karger Publishers Inc., Farmington, CT"},{"key":"2796_CR16","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1086\/301706","volume":"62","author":"T. Stankovic","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"2796_CR17","first-page":"2012","volume":"53","author":"S. Squires","year":"1993","journal-title":"Cancer Res."},{"key":"2796_CR18","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1093\/carcin\/15.5.823","volume":"15","author":"A. J. Ryan","year":"1994","journal-title":"Carcinogenesis"},{"key":"2796_CR19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/0165-4608(90)90245-6","volume":"50","author":"D. Morrell","year":"1990","journal-title":"Cancer Genet. Cytogenet."},{"key":"2796_CR20","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1056\/NEJM199112263252602","volume":"325","author":"M. Swift","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"2796_CR21","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1093\/jnci\/93.2.84","volume":"93","author":"M. Swift","year":"2001","journal-title":"J. Natl. Cancer I."},{"key":"2796_CR22","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1136\/bmj.317.7157.486","volume":"317","author":"M. Lavin","year":"1998","journal-title":"Br. Med. J."},{"key":"2796_CR23","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0165-4608(96)00328-7","volume":"92","author":"P. Athma","year":"1996","journal-title":"Cancer Genet. Cytogenet."},{"key":"2796_CR24","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/sj.bjc.6690209","volume":"79","author":"H. M. Inskip","year":"1999","journal-title":"Br. J. Cancer"},{"key":"2796_CR25","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/jnci\/93.2.121","volume":"93","author":"J. H. Olson","year":"2001","journal-title":"J. Natl. Cancer I"},{"key":"2796_CR26","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1056\/NEJM198705213162101","volume":"316","author":"M. Swift","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"2796_CR27","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/ng958","volume":"32","author":"K. Spring","year":"2002","journal-title":"Nat. Genet."},{"key":"2796_CR28","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1136\/jmg.40.12.e131","volume":"40","author":"K. Heikkinen","year":"2003","journal-title":"J. Med. Genet."},{"key":"2796_CR29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/jcb.10699","volume":"91","author":"A. Eastman","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"2796_CR30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0027-5107(94)90004-3","volume":"310","author":"T. K. Pandita","year":"1994","journal-title":"Mutat. Res."},{"key":"2796_CR31","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s004390050634","volume":"101","author":"A. Tchirkov","year":"1997","journal-title":"Hum. Genet."},{"key":"2796_CR32","first-page":"699","volume":"79","author":"C. S. Djuzenova","year":"1999","journal-title":"Lab. Invest."},{"key":"2796_CR33","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000056900","volume":"92","author":"M. Stumm","year":"2001","journal-title":"Cytogenet. Cell Genet."},{"key":"2796_CR34","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1667\/0033-7587(2002)157[0312:ROATAN]2.0.CO;2","volume":"157","author":"S. Neubauer","year":"2002","journal-title":"Radiat. Res."},{"key":"2796_CR35","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/sj.bjc.6601549","volume":"90","author":"M. Fernet","year":"2004","journal-title":"Br. J. Cancer"},{"key":"2796_CR36","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/gcc.20025","volume":"40","author":"S. Guti\u00e9rrez-Enriquez","year":"2004","journal-title":"Genes Chromosomes Cancer"}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/24\/6\/617\/472466\/bsr0240617.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/24\/6\/617\/472466\/bsr0240617.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T17:54:21Z","timestamp":1637085261000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/24\/6\/617\/54892\/Genome-Instability-in-Ataxia-Telangiectasia-A-T"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,1]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,12,1]]}},"URL":"https:\/\/doi.org\/10.1007\/s10540-005-2796-6","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,1]]}}}