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Cells have developed integrated double-strand break response pathways to cope with these lesions, including pathways that initiate DNA repair (either via homologous recombination or nonhomologous end joining), the cell-cycle checkpoints (G<jats:sub>1<\/jats:sub>\u2013S, intra-S phase, and G<jats:sub>2<\/jats:sub>\u2013M) that provide time for repair, and apoptosis. However, before any of these pathways can be activated, the damage must first be recognized. In this review, we will discuss how the response of mammalian cells to DNA double-strand breaks is regulated, beginning with the activation of ATM, the pinnacle kinase of the double-strand break signalling cascade. <\/jats:p>","DOI":"10.1139\/o07-135","type":"journal-article","created":{"date-parts":[[2007,11,30]],"date-time":"2007-11-30T17:56:37Z","timestamp":1196445397000},"page":"663-674","source":"Crossref","is-referenced-by-count":75,"title":["Regulation of the cellular DNA double-strand break response"],"prefix":"10.1139","volume":"85","author":[{"given":"Kendra L.","family":"Cann","sequence":"first","affiliation":[{"name":"MB Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E\u00a00V9, Canada."}]},{"given":"Geoffrey G.","family":"Hicks","sequence":"additional","affiliation":[{"name":"MB Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E\u00a00V9, Canada."}]}],"member":"155","reference":[{"key":"atypb1\/ref1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.20.5552"},{"key":"atypb2\/ref2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00010-6"},{"key":"atypb3\/ref3","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.5.1719-1729.2001"},{"key":"atypb4\/ref4","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgi319"},{"key":"atypb5\/ref5","doi-asserted-by":"publisher","DOI":"10.1038\/nature01368"},{"key":"atypb6\/ref6","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80086-0"},{"key":"atypb7\/ref7","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(00)00280-5"},{"key":"atypb8\/ref8","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02114-7"},{"key":"atypb9\/ref9","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1493"},{"key":"atypb10\/ref10","doi-asserted-by":"publisher","DOI":"10.1038\/387516a0"},{"key":"atypb11\/ref11","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5742(02)00009-1"},{"key":"atypb12\/ref12","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(02)00252-3"},{"key":"atypb13\/ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.016"},{"key":"atypb14\/ref14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100466200"},{"key":"atypb15\/ref15","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.4161\/cc.5.16.3009","volume":"5","author":"Cann K.L.","year":"2006","journal-title":"Cell Cycle"},{"key":"atypb16\/ref16","doi-asserted-by":"crossref","first-page":"596","DOI":"10.4161\/cc.2.6.502","volume":"2","author":"Cazzalini O.","year":"2003","journal-title":"Cell Cycle"},{"key":"atypb17\/ref17","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069398"},{"key":"atypb18\/ref18","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1004"},{"key":"atypb19\/ref19","doi-asserted-by":"publisher","DOI":"10.1038\/44188"},{"key":"atypb20\/ref20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.18.12748"},{"key":"atypb21\/ref21","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.21.7488-7497.2003"},{"key":"atypb22\/ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.05.126"},{"key":"atypb23\/ref23","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065521"},{"key":"atypb24\/ref24","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00063-0"},{"key":"atypb25\/ref25","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051923"},{"key":"atypb26\/ref26","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203283"},{"key":"atypb27\/ref27","first-page":"131","volume":"1602","author":"DeGregori J.","year":"2002","journal-title":"Biochim. 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