@article{d73a1575b60e436db00507f6dee1ef6d,
title = "Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2",
abstract = "BRCA2 mutations predispose carriers to breast and ovarian cancer and can also cause other cancers and Fanconi anemia. BRCA2 acts as a {"}caretaker{"} of genome integrity by enabling homologous recombination (HR)-based, error-free DNA double-strand break repair (DSBR) and intra-S phase DNA damage checkpoint control. Described here is the identification of PALB2, a BRCA2 binding protein. PALB2 colocalizes with BRCA2 in nuclear foci, promotes its localization and stability in key nuclear structures (e.g., chromatin and nuclear matrix), and enables its recombinational repair and checkpoint functions. In addition, multiple, germline BRCA2 missense mutations identified in breast cancer patients but of heretofore unknown biological/clinical consequence appear to disrupt PALB2 binding and disable BRCA2 HR/DSBR function. Thus, PALB2 licenses key cellular biochemical properties of BRCA2 and ensures its tumor suppression function.",
keywords = "CELLCYCLE, DNA",
author = "Bing Xia and Qing Sheng and Koji Nakanishi and Akihiro Ohashi and Jianmin Wu and Nicole Christ and Xinggang Liu and Maria Jasin and Couch, {Fergus J.} and Livingston, {David M.}",
note = "Funding Information: We thank J. Fryer for help in generating certain full-length BRCA2 encoding plasmids, R. Groisman and Y. Nakatani for providing the pOZ vectors, and A. Kung for advice on the usage of the pCMX-Gal4(N). We also thank L. Hughes-Davies and T. Kouzarides for providing EMSY antibodies. We are grateful to R. Drapkin, R. Greenberg, D. Silver, and Y. Yang for sharing reagents and for engaging in numerous, helpful discussions. This work was supported by the National Cancer Institute (D.M.L.), the Breast Cancer Program of U.S. Army Medical Research and Materiel Command (B.X.), the National Institutes of Health (M.J.), the Human Frontier Science Program (N.C.), American Cancer Society (F.J.C), and the Breast Cancer Research Foundation (F.J.C). One of us (D.M.L.) is a scientific consultant and research grant recipient of Novartis AG. ",
year = "2006",
month = jun,
day = "23",
doi = "10.1016/j.molcel.2006.05.022",
language = "English (US)",
volume = "22",
pages = "719--729",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}