The functional impact of BRCA1 BRCT domain variants using multiplexed DNA double-strand break repair assays

In this study, we used multiplexed DNA repair assays of variants in the BRCA1 carboxy-terminus to functionally characterize 2271 variants for homology-directed repair function (HDR) and 1427 variants for cisplatin resistance (CR). We found a high level of consistent results in the two multiplexed functional assays with non-functional variants located within regions of the BRCA1 protein necessary for its tumor suppression activity. In this study, we have analyzed the BRCA1 carboxy-terminus for the functional impact of single missense substitutions using two multiplexed assays: homology directed repair of DNA double stranded breaks and resistance to cisplatin. HDR is for homology-directed repair, CR is for the cisplatin treatment, and GL2 is for the control siRNA condition used.