{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:57:32Z","timestamp":1791320252266,"version":"4.3.1"},"reference-count":196,"publisher":"Annual Reviews","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annu. Rev. Genom. Hum. Genet."],"published-print":{"date-parts":[[2007,9,1]]},"abstract":"<jats:p> Each day tens of thousands of DNA single-strand breaks (SSBs) arise in every cell from the attack of deoxyribose and DNA bases by reactive oxygen species and other electrophilic molecules. DNA double-strand breaks (DSBs) also arise, albeit at a much lower frequency, from similar attacks and from the encounter of unrepaired SSBs and possibly other DNA structures by DNA replication forks. DSBs are also created during normal development of the immune system. Defects in the cellular response to DNA strand breaks underpin many human diseases, including disorders associated with cancer predisposition, immune dysfunction, radiosensitivity, and neurodegeneration. Here we provide an overview of the genetic diseases associated with defects in the repair\/response to DNA strand breaks. <\/jats:p>","DOI":"10.1146\/annurev.genom.7.080505.115648","type":"journal-article","created":{"date-parts":[[2007,9,21]],"date-time":"2007-09-21T18:46:23Z","timestamp":1190400383000},"page":"37-55","source":"Crossref","is-referenced-by-count":272,"title":["DNA Strand Break Repair and Human Genetic Disease"],"prefix":"10.1146","volume":"8","author":[{"given":"Peter J.","family":"McKinnon","sequence":"first","affiliation":[{"name":"Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith W.","family":"Caldecott","sequence":"additional","affiliation":[{"name":"Genome Damage and Stability Center, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"22","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05164"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.12.031"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1431"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1196104"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9107"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.11.028"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(01)00269-6"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature01368"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205200"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90450-Q"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-7864(01)00007-6"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122228699"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30869"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000276200"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00030-1"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1021\/bi025942q"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.12.030"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600563"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100466200"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01247-3"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-7864(03)00118-6"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308717101"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00304-X"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81175-7"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg630"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1004"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.11.2827"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80276-2"},{"key":"B29","first-page":"1752s","volume":"59","author":"Chen JJ","year":"1999","journal-title":"Cancer Res."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.04.010"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.06.017"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208332"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5442.1162"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207191"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3420249"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nrm805"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-184"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00175-7"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.028795"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl010"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1270"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.7.1121"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207937200"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh649"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00424-6"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/nature03314"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nature03404"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ncb884"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.21.2591"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg274"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01052-8"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00173-3"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1385\/CRIAI:20:1:87"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh274"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601255"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400255"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403221"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02371-0"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000881200"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608727200"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/nature00922"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi065"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073834"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.6.637"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00930-9"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2006.02.007"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh135"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg266"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkf482"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/nature03097"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1101\/gad.970602"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1200304"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603290200"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5433.1576"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1269\/jrr.45.473"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600375"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00367-8"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601231"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.131009198"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-238"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1126\/science.1091496"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1126\/science.1108297"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/35004614"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1101\/gad.837100"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2003.10.011"},{"key":"B86","first-page":"6343","volume":"48","author":"Lehmann AR","year":"1988","journal-title":"Cancer Res."},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/ng1624"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1202"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507722102"},{"key":"B90","unstructured":"Deleted in proof"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.08.004"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182557199"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1101\/gad.279003"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.5.1949-1957.2005"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1038\/ncb945"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.19.8356-8365.2004"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.11.017"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00671-2"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.17.11550"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/76950"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.7.4633"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.08.018"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400210"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205742"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1126\/science.7545954"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)01632-7"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-189"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1038\/nature03927"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.3.463"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00309-9"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200316774"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2003.12.003"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80202-6"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00174-5"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1038\/ncb879"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407796102"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.9.2996-3003.2000"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.12.009"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.2307\/3579256"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00408-7"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.025"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00610-2"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1038\/nature01230"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1038\/nature05112"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(03)00170-3"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(03)00170-3"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.21.2531"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-7864(03)00116-2"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2001.00452.x"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.2.609"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.10.029"},{"key":"B132","unstructured":"Deleted in proof"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.10.5858"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01625-8"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021891"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074740"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10808"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.17.7444-7455.2004"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051632098"},{"key":"B140","first-page":"1","volume":"13","author":"Shao N","year":"1996","journal-title":"Oncogene"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1011"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203334"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.2.425-437.2006"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1016\/0921-8777(93)90057-N"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(03)00042-5"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81547-0"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1038\/nature01446"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504211102"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1007\/BF01232819"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1038\/ng987"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0278"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.04.009"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/4.5.559"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.2.195"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005824200"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00455-6"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(99)00058-0"},{"key":"B158","first-page":"3325","volume":"63","author":"Thorstenson YR","year":"2003","journal-title":"Cancer Res."},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1101\/gad.851000"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13823-8"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1038\/ng1484"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.17.4704"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg541"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.embor925"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202242599"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202242599"},{"key":"B167","first-page":"270","volume":"61","author":"Wang H","year":"2001","journal-title":"Cancer Res."},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2005.02.001"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.13.5850-5862.2004"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1080\/01926230490424680"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041010211"},{"key":"B172","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1127"},{"key":"B173","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.21.7926-7936.2003"},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00763-7"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.1139\/o05-153"},{"key":"B176","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb928"},{"key":"B177","doi-asserted-by":"publisher","DOI":"10.1038\/378789a0"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21428"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.1038\/ng1296-430"},{"key":"B180","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151253498"},{"key":"B181","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.23.8668-8690.2003"},{"key":"B182","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400139200"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.1.34-43.2005"},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.15.5421-5430.2003"},{"key":"B185","doi-asserted-by":"publisher","DOI":"10.1126\/science.297.5588.1837"},{"key":"B186","doi-asserted-by":"publisher","DOI":"10.1038\/nature03234"},{"key":"B187","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgi134"},{"key":"B188","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00394-0"},{"key":"B189","first-page":"3547","volume":"59","author":"Yuan SS","year":"1999","journal-title":"Cancer Res."},{"key":"B190","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.20.9207-9220.2004"},{"key":"B191","first-page":"3966","volume":"62","author":"Zhong Q","year":"2002","journal-title":"Cancer Res."},{"key":"B192","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200748200"},{"key":"B193","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.747"},{"key":"B194","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.14.6601"},{"key":"B195","doi-asserted-by":"publisher","DOI":"10.1021\/bi00253a032"},{"key":"B196","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90030-6"}],"container-title":["Annual Review of Genomics and Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.annualreviews.org\/doi\/pdf\/10.1146\/annurev.genom.7.080505.115648","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T16:44:26Z","timestamp":1634057066000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.annualreviews.org\/doi\/10.1146\/annurev.genom.7.080505.115648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,1]]},"references-count":196,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,9,1]]}},"alternative-id":["10.1146\/annurev.genom.7.080505.115648"],"URL":"https:\/\/doi.org\/10.1146\/annurev.genom.7.080505.115648","relation":{},"ISSN":["1527-8204","1545-293X"],"issn-type":[{"value":"1527-8204","type":"print"},{"value":"1545-293X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,9,1]]}}}