Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2

Bing Xia, Qing Sheng, Koji Nakanishi, Akihiro Ohashi, Jianmin Wu, Nicole Christ, Xinggang Liu, Maria Jasin, Fergus J. Couch, David M. Livingston

Research output: Contribution to journalArticlepeer-review

531 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)719-729
Number of pages11
JournalMolecular Cell
Volume22
Issue number6
DOIs
StatePublished - Jun 23 2006

Keywords

  • CELLCYCLE
  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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