{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T20:37:36Z","timestamp":1775767056054,"version":"3.50.1"},"reference-count":25,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5645","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,10,24]]},"abstract":"<jats:p>\n                    We used a proteomic approach to identify phosphopeptide-binding modules mediating signal transduction events in the DNA damage response pathway. Using a library of partially degenerate phosphopeptides, we identified tandem BRCT (BRCA1 carboxyl-terminal) domains in PTIP (Pax transactivation domain-interacting protein) and in BRCA1 as phosphoserine- or phosphothreonine-specific binding modules that recognize substrates phosphorylated by the kinases ATM (ataxia telangiectasia\u2013mutated) and ATR(ataxia telangiectasia\u2013 and RAD3-related) in response to \u03b3-irradiation. PTIP tandem BRCT domains are responsible for phosphorylation-dependent protein localization into 53BP1- and phospho-H2AX (\u03b3-H2AX)\u2013containing nuclear foci, a marker of DNA damage. These findings provide a molecular basis for BRCT domain function in the DNA damage response and may help to explain why the BRCA1 BRCT domain mutation Met\n                    <jats:sup>1775<\/jats:sup>\n                    \u2192 Arg, which fails to bind phosphopeptides, predisposes women to breast and ovarian cancer.\n                  <\/jats:p>","DOI":"10.1126\/science.1088877","type":"journal-article","created":{"date-parts":[[2003,10,23]],"date-time":"2003-10-23T22:34:42Z","timestamp":1066948482000},"page":"636-639","source":"Crossref","is-referenced-by-count":547,"title":["BRCT Repeats As Phosphopeptide-Binding Modules Involved in Protein Targeting"],"prefix":"10.1126","volume":"302","author":[{"given":"Isaac A.","family":"Manke","sequence":"first","affiliation":[{"name":"Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}]},{"given":"Drew M.","family":"Lowery","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}]},{"given":"Anhco","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}]},{"given":"Michael B.","family":"Yaffe","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083653"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35044005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm759"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(00)00189-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079079"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.914401"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.53.37538"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001002200"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.14.2741"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.5.1666-1673.2003"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.12.3901-3912.2001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(00)00034-3"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb1001-838"},{"key":"e_1_3_2_15_2","first-page":"4375","volume":"59","year":"1999","unstructured":"J. N. Sarkariaet al., Cancer Res.59, 4375 (1999).","journal-title":"Cancer Res."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.7.1381"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.153.3.613"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1076182"},{"key":"e_1_3_2_19_2","unstructured":"I. A. Manke D. M. Lowery A. Nguyen M. B. Yaffe unpublished data."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/35044000"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210019200"},{"key":"e_1_3_2_22_2","unstructured":"See supporting data on Science Online."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.1.260"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(00)28397-3"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80486-2"},{"key":"e_1_3_2_26_2","unstructured":"We thank K. Hoepker and A. Elia for participation at early stages in this work T. Ho and S. Bissonnette for figure construction D. Rubinson and J. Loureiro for assistance with microscopy R. Grant for assistance with protein purification J. Robbins for critical reading of the manuscript R. T. Abraham for discussions and J. Chen for sharing unpublished data. The MDC1 53BP1 and Brca1 plasmids were gifts from S. J. Elledge K. Iwabuchi and D. Livingston respectively. D.M.L. is a Howard Hughes Medical Institute predoctoral fellow. Supported by NIH grant GM60594 and a Burroughs-Wellcome Career Development Award (M.B.Y.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1088877","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:46:23Z","timestamp":1704836783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1088877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10,24]]},"references-count":25,"journal-issue":{"issue":"5645","published-print":{"date-parts":[[2003,10,24]]}},"alternative-id":["10.1126\/science.1088877"],"URL":"https:\/\/doi.org\/10.1126\/science.1088877","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1006565.199512","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10,24]]}}}