2. Academic Validation
  3. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2

Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2

  • Mol Cell. 2006 Jun 23;22(6):719-729. doi: 10.1016/j.molcel.2006.05.022.
Bing Xia 1,  Qing Sheng 1,  Koji Nakanishi 2,  Akihiro Ohashi 3,  Jianmin Wu 3,  Nicole Christ 2,  Xinggang Liu 1,  Maria Jasin 2,  Fergus J Couch 3,  David M Livingston 4
Affiliations

Affiliations

  • 1 Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115.
  • 2 Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021.
  • 3 Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, Minnesota 55905.
  • 4 Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115. Electronic address: david_livingston@dfci.harvard.edu.
PMID: 16793542 DOI: 10.1016/j.molcel.2006.05.022
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.

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