Specificity
In 1990, a breast cancer susceptibility gene designated BRCA1 was localized to chromosome 17q. Mutations within this gene are believed to account for approximately 45% of families with high incidence of breast cancer and at least 80% of families with increased incidence of both early-onset breast cancer and ovarian cancer. A second breast cancer susceptibility gene, BRCA2 (breast cancer 2, early onset), located on chromosome 13q13.1, also confers a high incidence of breast cancer but, unlike BRCA1, does not confer a substantially elevated risk of ovarian cancer. Both BRCA1 and BRCA2 play a role in the maintainance of genome stability, particularly in the homologous recombination pathway for double-strand DNA repair. BRCA2 is regarded as a tumor suppressor gene; tumors with BRCA2 mutations exhibit loss of heterozygosity (LOH) of the wildtype allele. The protein encoded by the BRCA2 gene contains multiple copies of a 70 amino acid motif called the BRC motif. These motifs effect binding to the Rad51 recombinase, which operates in DNA repair.
