Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2 Journal Article
| Authors: | Xia, B.; Sheng, Q.; Nakanishi, K.; Ohashi, A.; Wu, J.; Christ, N.; Liu, X.; Jasin, M.; Couch, F. J.; Livingston, D. M. |
| Article 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. © 2006 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; mutation, missense; cancer patient; chemical analysis; ovarian neoplasms; protein analysis; dna damage; dna repair; genetic predisposition to disease; breast cancer; protein binding; protein stability; hela cells; breast neoplasms; brca2 protein; nuclear proteins; cancer inhibition; dna; chromatin; recombination, genetic; tumor suppressor proteins; binding protein; cellcycle; cytochemistry; s phase; germ-line mutation; palb2 protein; cell nucleus matrix; nuclear matrix |
| Journal Title: | Molecular Cell |
| Volume: | 22 |
| Issue: | 6 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2006-06-23 |
| Start Page: | 719 |
| End Page: | 729 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2006.05.022 |
| PUBMED: | 16793542 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 182" - "Export Date: 4 June 2012" - "CODEN: MOCEF" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work