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

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.

Pubmed ID: 16793542

Authors

  • Xia B
  • Sheng Q
  • Nakanishi K
  • Ohashi A
  • Wu J
  • Christ N
  • Liu X
  • Jasin M
  • Couch FJ
  • Livingston DM

Journal

Molecular cell

Publication Data

June 23, 2006

Associated Grants

None

Mesh Terms

  • BRCA2 Protein
  • Breast Neoplasms
  • Chromatin
  • DNA Damage
  • DNA Repair
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • HeLa Cells
  • Humans
  • Mutation, Missense
  • Nuclear Matrix
  • Nuclear Proteins
  • Ovarian Neoplasms
  • Protein Binding
  • Recombination, Genetic
  • S Phase
  • Tumor Suppressor Proteins