Deciphering the BRCA1 Tumor Suppressor Network

Abstract The BRCA1 tumor suppressor proteinis a central constituent of several distinct macromolecular protein complexes that execute homology- directed DNA damagerepair and cell cycle checkpoints. Recent years have borne witness to an exciting phase of discovery at the basic molecular level for how this network of DNA repair proteins acts to maintain genome stability and suppress cancer. The clinical dividends of this investment are now being realized with the approval of first-in-class BRCA- targeted therapiesfor ovarian cancer and identification of molecular events that determine responsiveness to these agents. Further delineation of the basic scienceunderlying BRCA network function holds promise to maximally exploit genome instabilityfor hereditary and sporadic cancer therapy.