{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:30:24Z","timestamp":1792456224896,"version":"4.5.0"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Poly(ADP-ribose) polymerase (PARP) inhibitors have produced responses in homologous recombination (HR) repair-deficient cancers, such as those with a mutated breast cancer 1, early onset (\n                    <jats:italic>BRCA1<\/jats:italic>\n                    ) gene. We have delineated a two-event mechanism of acquired resistance by using a\n                    <jats:italic>BRCA1<\/jats:italic>\n                    BRCA C-terminal (BRCT) domain-mutated breast cancer cell line, involving heat shock protein (HSP)90-mediated stabilization of the mutant protein coupled with tumor protein p53 binding protein 1 (\n                    <jats:italic>TP53BP1<\/jats:italic>\n                    ) gene mutation, which together restore DNA end resection and RAD51 filament formation, critical steps in HR. Similar events may occur in primary\n                    <jats:italic>BRCA1<\/jats:italic>\n                    -mutated ovarian cancers as cells develop resistance to platinum. The data demonstrate that, even though BRCA1 BRCT domain mutant proteins cannot promote DNA end resection, they retain partial function and can contribute to RAD51 loading and HR. Finally, HSP90 inhibition may prove useful for resensitizing resistant\n                    <jats:italic>BRCA1<\/jats:italic>\n                    -mutant cancer cells to drug treatment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1305170110","type":"journal-article","created":{"date-parts":[[2013,10,2]],"date-time":"2013-10-02T00:24:52Z","timestamp":1380673492000},"page":"17041-17046","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":251,"title":["Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance"],"prefix":"10.1073","volume":"110","author":[{"given":"Neil","family":"Johnson","sequence":"first","affiliation":[{"name":"Departments of aMedical Oncology,"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn F.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Departments of aMedical Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yao","sequence":"additional","affiliation":[{"name":"Departments of aMedical Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chen","family":"Li","sequence":"additional","affiliation":[{"name":"Departments of aMedical Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Eun","family":"Choi","sequence":"additional","affiliation":[{"name":"Radiation Oncology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea J.","family":"Bernhardy","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wang","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Capelletti","sequence":"additional","affiliation":[{"name":"Departments of aMedical Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristopher A.","family":"Sarosiek","sequence":"additional","affiliation":[{"name":"Departments of aMedical Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Moreau","sequence":"additional","affiliation":[{"name":"Radiation Oncology, and"},{"name":"Department of Pediatrics, Children\u2019s Hospital and Harvard Medical School, Boston, MA 02215; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipanjan","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Radiation Oncology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneka","family":"Wickramanayake","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology and Medicine, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Harrell","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology and Medicine, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce F.","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of aMedical Oncology,"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan D.","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"Radiation Oncology, and"},{"name":"Department of Pediatrics, Children\u2019s Hospital and Harvard Medical School, Boston, MA 02215; 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