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To explore the effect of clinically relevant\n                    <jats:italic>ATM<\/jats:italic>\n                    mutations, we characterized DSBR between mutated\n                    <jats:italic>EGFP<\/jats:italic>\n                    genes and ATM kinase signaling in 9 lymphoblastoid cell lines (LCLs) derived from patients with ataxia telangiectasia (AT) with defined\n                    <jats:italic>vs.<\/jats:italic>\n                    3 control LCLs without\n                    <jats:italic>ATM<\/jats:italic>\n                    mutations. Our study revealed that the DSBR phenotype in AT cells is not uniform but appears to depend on the mutation, causing up to 32\u2010fold increased or up to 3\u2010fold decreased activities in particular pathways. Comparison with a further 10 LCLs mutated in downstream factors (BRCA1, BRCA2, Nibrin, Rad50, and Chk2) showed that the most diametrically opposed DSBR patterns in AT cells phenocopied\n                    <jats:italic>NBN\/RAD50<\/jats:italic>\n                    or\n                    <jats:italic>BRCA1<\/jats:italic>\n                    mutations. Notably, reexpressing wild\u2010type ATM reversed these defects by 2.3\u2010 to 3.5\u2010fold. Our data suggest that ATM stimulates repair proteins such as Nibrin, which execute HR, single\u2010strand annealing (SSA), and NHEJ. Concomitantly, ATM minimizes error\u2010prone repair (SSA and NHEJ) through activation of surveillance factors such as BRCA1. Since the outcome of the individual defect can be diametrically opposed, distinguishing repair patterns in patients with\n                    <jats:italic>ATM<\/jats:italic>\n                    mutations may also be relevant regarding therapeutic responses.\u2014Keimling, M., Volcic, M., Csernok, A., Wieland, B., D\u00f6rk, T., Wiesm\u00fcller, L. Functional characterization connects individual patient mutations in\n                    <jats:italic>ataxia telangiectasia mutated (ATM)<\/jats:italic>\n                    with dysfunction of specific DNA double\u2010strand break\u2010repair signaling pathways.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 3849\u20133860 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-185546","type":"journal-article","created":{"date-parts":[[2011,7,21]],"date-time":"2011-07-21T22:27:49Z","timestamp":1311287269000},"page":"3849-3860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Functional characterization connects individual patient mutations in\n                    <i>ataxia telangiectasia mutated (ATM)<\/i>\n                    with dysfunction of specific DNA double\u2010strand break\u2010repair signaling pathways"],"prefix":"10.1096","volume":"25","author":[{"given":"Marlen","family":"Keimling","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meta","family":"Volcic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Csernok","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Wieland","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit Hannover Medical School  Hannover Germany"},{"name":"Department of Radiation Oncology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"D\u00f6rk","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Wiesm\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,7,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2514"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.1.69"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20101"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.01.010"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210873"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.569"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210876"},{"key":"e_1_2_6_9_1","first-page":"395","article-title":"Atm deficiency causes increased frequency of intrachro\u2010mosomal homologous recombination in mice","volume":"60","author":"Bishop A. 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