BRCA1 in breast and ovarian cancer predisposition

Women carrying one mutated BRCA1 allele are at increased risk of developing breast and ovarian cancer but tumor initiation requires the loss of the wild-type allele indicating that it is a tumor suppressor gene. In the 10 years since the cloning of BRCA1, a function for the gene product in the DNA damage response has been established. However, identifying the exact biochemical activities of BRCA1 has been a more difficult task. Our current understanding suggests that the molecular functions mediated by the terminal ends of BRCA1, which include an E3 ubiquitin ligase activity at the N-terminus and a protein-protein interaction surface at the C-terminus, are critical to the function of this protein in the response to DNA damage. (C) 2004 Elsevier Ireland Ltd. All rights reserved.