Role of BRCA2 in Control of the RAD51 Recombination and DNA Repair Protein

Mol Cell. 2001 Feb;7(2):273-82. doi: 10.1016/s1097-2765(01)00175-7.

Abstract

Individuals carrying BRCA2 mutations are predisposed to breast and ovarian cancers. Here, we show that BRCA2 plays a dual role in regulating the actions of RAD51, a protein essential for homologous recombination and DNA repair. First, interactions between RAD51 and the BRC3 or BRC4 regions of BRCA2 block nucleoprotein filament formation by RAD51. Alterations to the BRC3 region that mimic cancer-associated BRCA2 mutations fail to exhibit this effect. Second, transport of RAD51 to the nucleus is defective in cells carrying a cancer-associated BRCA2 truncation. Thus, BRCA2 regulates both the intracellular localization and DNA binding ability of RAD51. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • BRCA2 Protein
  • Binding Sites
  • Breast Neoplasms / genetics
  • Chromatography, Gel
  • DNA / genetics
  • DNA / metabolism
  • DNA Repair / genetics*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Microscopy, Electron
  • Models, Biological
  • Molecular Sequence Data
  • Molecular Weight
  • Mutation
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nucleoproteins / antagonists & inhibitors
  • Nucleoproteins / metabolism
  • Nucleoproteins / ultrastructure
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology
  • Protein Binding
  • Protein Structure, Tertiary
  • Rad51 Recombinase
  • Recombination, Genetic*
  • Subcellular Fractions
  • Substrate Specificity
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • BRCA2 Protein
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Nucleoproteins
  • Peptide Fragments
  • Transcription Factors
  • DNA
  • RAD51 protein, human
  • Rad51 Recombinase