Functional domains of the BRCA1 and BRCA2 proteins.

The BRCA1 and BRCA2 genes encode large unrelated proteins that presumably function as tumor suppressors in normal epithelial cells of the breast. However, the primary amino acid sequences of these proteins provide few insights into the mechanisms by which BRCA1 and BRCA2 inhibit tumor development. Nevertheless, recent studies have uncovered many similarities in the biological properties of BRCA1 and BRCA2, raising the prospect that these proteins may function in a common pathway of tumor suppression and that inactivation of either gene may represent an equivalent step in the development of breast cancer. Several lines of evidence now suggest a role for BRCA1 and BRCA2 in the cellular response to DNA damage, possibly by virtue of their relationship with proteins required for the recombinational repair of double-strand DNA breaks. Accordingly, the loss of BRCA1 or BRCA2 function might accelerate tumor development by allowing cells to accumulate DNA lesions that are potentially oncogenic.