BRCA1 is an essential component of multiple distinct protein complexes that are dedicated to DNA damage recognition and repair. Germline heterozygous mutations to genes encoding multiple BRCA associated proteins result in cancer susceptibility, while biallelic mutations lead to developmental abnormalities, cancer predisposition, and systemic hypersensitivity to chemotherapy. BRCA1 associates with the RAP80 complex to recognize lysine63-linked ubiquitin chains at DNA damage sites. Three members of the RAP80 complex are mutated in hereditary breast cancer, implicating ubiquitin recognition as a bona fide component of BRCA1 dependent tumor suppression. This presentation will describe in vivo interactions between BRCA1 associated DNA damage site ubiquitin recognition and other protein complexes that are dedicated to homologous recombination mediated DNA repair to S-phase. Relevance to cancer etiology and response to therapy will be discussed.
Citation Format: Roger A. Greenberg. The BRCA1 tumor suppressor network. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr IA23. doi:10.1158/1538-7445.CANSUSC14-IA23