Mutations within the BRCA1 gene, localized to chromosome 17q, are believed to account for approximately 45% of families with increased incidence of both early-onset breast cancer and ovarian cancer. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a RING domain near the N-terminus and appears to encode a tumor suppressor. BARD1 (BRCA1-associated RING domain protein 1) and BAP1 (BRCA1-associated protein 1) have both been shown to bind to the N-terminus of BRCA1 and are potential mediators of tumor suppression. BARD1 contains an N-terminal RING domain and three tandem ankyrin repeats. The C-terminus of BARD1 contains a region with sequence homology to BRCA1, termed the BRCT domain. BAP1 is a ubiquitin hydrolase and has been shown to enhance BRCA1-mediated cell growth suppression.
