BRCA1 and BRCA2: different roles in a common pathway of genome protection

Nat Rev Cancer. 2011 Dec 23;12(1):68-78. doi: 10.1038/nrc3181.


The proteins encoded by the two major breast cancer susceptibility genes, BRCA1 and BRCA2, work in a common pathway of genome protection. However, the two proteins work at different stages in the DNA damage response (DDR) and in DNA repair. BRCA1 is a pleiotropic DDR protein that functions in both checkpoint activation and DNA repair, whereas BRCA2 is a mediator of the core mechanism of homologous recombination. The links between the two proteins are not well understood, but they must exist to explain the marked similarity of human cancer susceptibility that arises with germline mutations in these genes. As discussed here, the proteins work in concert to protect the genome from double-strand DNA damage during DNA replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • BRCA1 Protein / chemistry
  • BRCA1 Protein / physiology*
  • BRCA2 Protein / chemistry
  • BRCA2 Protein / physiology*
  • Breast Neoplasms / etiology
  • Breast Neoplasms / genetics
  • DNA Damage*
  • DNA Repair
  • Fanconi Anemia Complementation Group N Protein
  • Female
  • Genomic Instability
  • Homologous Recombination
  • Humans
  • Loss of Heterozygosity
  • Mice
  • Nuclear Proteins / physiology
  • Ovarian Neoplasms / etiology
  • Ovarian Neoplasms / genetics
  • Protein Structure, Tertiary
  • Tumor Suppressor Protein p53 / physiology
  • Tumor Suppressor Proteins / physiology


  • BRCA1 Protein
  • BRCA2 Protein
  • Fanconi Anemia Complementation Group N Protein
  • Nuclear Proteins
  • PALB2 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins