The relationship between the roles of BRCA genes in DNA repair and cancer predisposition.

The proteins encoded by the breast-cancer-susceptibility genes, BRCA1 and BRCA2, have recently been implicated in DNA-repair processes, thereby improving our understanding of how the loss of these genes contributes to cancer initiation and progression. It appears that the role of BRCA1 in DNA repair, which could involve the integration of several pathways, is broader than that of BRCA2. BRCA1 functions in the signalling of DNA damage and its repair by homologous recombination, nucleotide-excision repair and possibly non-homologous end-joining. BRCA2 has a more specific role in DNA repair, regulating the activity of RAD51, which is required for homologous recombination. An improved understanding of the interactions of BRCA1 and BRCA2 with other proteins in large macromolecular complexes is helping to reveal their exact role in DNA repair.