Deciphering the BRCA1 Tumor Suppressor Network

J Biol Chem. 2015 Jul 17;290(29):17724-17732. doi: 10.1074/jbc.R115.667931. Epub 2015 Jun 5.

Abstract

The BRCA1 tumor suppressor protein is a central constituent of several distinct macromolecular protein complexes that execute homology-directed DNA damage repair and cell cycle checkpoints. Recent years have borne witness to an exciting phase of discovery at the basic molecular level for how this network of DNA repair proteins acts to maintain genome stability and suppress cancer. The clinical dividends of this investment are now being realized with the approval of first-in-class BRCA-targeted therapies for ovarian cancer and identification of molecular events that determine responsiveness to these agents. Further delineation of the basic science underlying BRCA network function holds promise to maximally exploit genome instability for hereditary and sporadic cancer therapy.

Keywords: BRCA1; BRCA2; DNA damage response; DNA repair; breast cancer.

Publication types

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

MeSH terms

  • Animals
  • BRCA1 Protein / analysis
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism*
  • Breast / metabolism
  • Breast / pathology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • DNA Damage
  • DNA Repair*
  • Female
  • Genomic Instability
  • Humans
  • Molecular Targeted Therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy
  • Ovary / metabolism
  • Ovary / pathology
  • Protein Interaction Maps

Substances

  • BRCA1 Protein