We are interested in the relationship between recombination and cancer, with particular focus on the hereditary breast/ovarian cancer predisposition genes, BRCA1 and BRCA2. BRCA1 and BRCA2 are required for efficient homologous recombination and double strand break repair, mediated by interactions with the recombination protein, Rad51. Circumstantial evidence suggests a role for BRCA1, BRCA2 and Rad51in controlling recombination between sister chromatids during DNA synthesis. This is thought to be initiated by the stalling of a DNA polymerase complex upon its encounter with abnormal DNA structure. In order to examine the role of BRCA1 and BRCA2 in sister chromatid recombination, we have developed a novel reporter for this process. We have used this reporter to identify sister chromatid recombination events in cells cultured in vitro, by means of a simple positive selection step. We can now analyze sister chromatid recombination in relation to BRCA gene function in molecular detail. For example, we are using the reporter to obtain DNA sequence across break-points of spontaneous sister chromatid recombination events occurring in BRCA gene mutant or in wild-type cells - information that has not previously been accessible to study. We are also using the positive selective power of the reporter to clone new genes that control sister chromatid recombination. Genes identified using this approach may themselves be cancer susceptibility genes.