We are interested in the hereditary breast/ovarian cancer predisposition syndromes, with particular emphasis upon the basic biology of BRCA1 and BRCA2. Each gene product interacts with the Rad51 recombinase, a protein with a central role in homologous recombination. Consistent with this, dysfunction in either BRCA1 or BRCA2 produces chromosome breakage and profound genomic instability. Circumstantial evidence suggests that the BRCA1/BRCA2/Rad51 complex acts particulary during the S and G2 phases of the cell cycle, suggesting a potential role in sister chromatid recombination. We are using biochemical and genetic approaches in an effort to determine precisely how BRCA1 and BRCA2 regulate Rad51 functions and to understand the relationship between recombination and breast/ovarian cancer. As part of this work, we have devised novel assays for quantifying recombination between sister chromatids, and are currently applying them in the study of BRCA1 and BRCA2 function.