FUNCTIONAL DOMAINS OF THE BRCA1 AND BRCA2 PROTEINS

The BRCA1 and BRCA2 genes encode large unrelated proteins that presuma bly function as tumor suppressors in normal epithelial cells of the br east. However, the primary amino acid sequences of these proteins prov ide few insights into the mechanisms by which BRCA1 and BRCA2 inhibit tumor development. Nevertheless, recent studies have uncovered many si milarities in the biological properties of BRCA1 and BRCA2, raising th e prospect that these proteins may function in a common pathway of tum or suppression and that inactivation of either gene may represent an e quivalent step in the development of breast cancer. Several lines of e vidence now suggest a role for BRCA1 and BRCA2 in the cellular respons e to DNA damage, possibly by virtue of their relationship with protein s required for the recombinational repair of double-strand DNA breaks. Accordingly, the loss of BRCA1 or BRCA2 function might accelerate tum or development by allowing cells to accumulate DNA lesions that are po tentially oncogenic.