Homologous repair of DNA damage and tumorigenesis: the BRCA connection

Homologous recombination has been recognized in recent years to be an important DNA repair pathway in mammalian cells, for such damage as chromosomal double-strand breaks. Cells mutated for the genes involved in the hereditary breast and ovarian cancer susceptibility syndromes, i.e. BRCAJ and BRCA2, show defects in DNA repair by homologous recombination, implicating this repair pathway in protecting individuals against tumorigenesis. This review summarizes recent advances in our understanding of BRCA1 and BRCA2 in DNA repair, as well as insight into these proteins gleaned from structure determination of domains of these proteins and the broader evolutionary conservation than previously appreciated.