{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:09:45Z","timestamp":1790064585218,"version":"4.0.1"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,5,21]]},"abstract":"\n Germ-line mutations in\n PALB2<\/jats:italic>\n lead to a familial predisposition to breast and pancreatic cancer or to Fanconi Anemia subtype N. PALB2 performs its tumor suppressor role, at least in part, by supporting homologous recombination-type double strand break repair (HR-DSBR) through physical interactions with BRCA1, BRCA2, and RAD51. To further understand the mechanisms underlying PALB2-mediated DNA repair and tumor suppression functions, we targeted\n Palb2<\/jats:italic>\n in the mouse.\n Palb2<\/jats:italic>\n -deficient murine ES cells recapitulated DNA damage defects caused by PALB2 depletion in human cells, and germ-line deletion of\n Palb2<\/jats:italic>\n led to early embryonic lethality. Somatic deletion of\n Palb2<\/jats:italic>\n driven by\n K14-<\/jats:italic>\n Cre led to mammary tumor formation with long latency. Codeletion of both\n Palb2<\/jats:italic>\n and Tumor protein 53 (\n Trp53<\/jats:italic>\n ) accelerated mammary tumor formation. Like\n BRCA1<\/jats:italic>\n and\n BRCA2<\/jats:italic>\n mutant breast cancers, these tumors were defective in RAD51 focus formation, reflecting a defect in\n Palb2<\/jats:italic>\n HR-DSBR function, a strongly suspected contributor to\n Brca1, Brca2<\/jats:italic>\n , and\n Palb2<\/jats:italic>\n mammary tumor development. However, unlike the case of\n Brca1<\/jats:italic>\n -mutant cells,\n Trp53bp1<\/jats:italic>\n deletion failed to rescue the genomic instability of\n Palb2<\/jats:italic>\n - or\n Brca2<\/jats:italic>\n -mutant primary lymphocytes. Therefore,\n Palb2<\/jats:italic>\n -driven DNA damage control is, in part, distinct from that executed by\n Brca1<\/jats:italic>\n and more similar to that of\n Brca2.<\/jats:italic>\n The mechanisms underlying\n Palb2<\/jats:italic>\n mammary tumor suppression functions can now be explored genetically in vivo.\n <\/jats:p>","DOI":"10.1073\/pnas.1305362110","type":"journal-article","created":{"date-parts":[[2013,5,9]],"date-time":"2013-05-09T00:14:46Z","timestamp":1368058486000},"page":"8632-8637","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Palb2<\/i>\n synergizes with\n Trp53<\/i>\n to suppress mammary tumor formation in a model of inherited breast cancer"],"prefix":"10.1073","volume":"110","author":[{"given":"Christian","family":"Bowman-Colin","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Xia","sequence":"additional","affiliation":[{"name":"Cancer Institute of New Jersey, New Brunswick, NJ 08901;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Bunting","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan","family":"Klijn","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinske","family":"Drost","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bouwman","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fineman","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aedin C.","family":"Culhane","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215;"},{"name":"Biostatistics, Harvard School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Cai","sequence":"additional","affiliation":[{"name":"Cancer Institute of New Jersey, New Brunswick, NJ 08901;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Rodig","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick T.","family":"Bronson","sequence":"additional","affiliation":[{"name":"Rodent Histology Core, Dana-Farber\/Harvard Cancer Center, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos","family":"Jonkers","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The 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