BRCA 1-Mediated Histone Monoubiquitylation: Effect on Nucleosome Dynamics; Final rept. 24 Jul 2006-23 Jan 2008

摘要

BRCA1, the protein product of the Breast Cancer Susceptibility Gene (BRCA1) has been implicated in multiple pathways that preserve genome stability, including cell cycle control, DNA repair, transcription, and chromatin remodeling. BRCA1, in complex with another RING-domain protein BARD1, possesses ubiquitin-ligase activity. Only a few targets for this activity have been identified in vivo. Nucleosomal histones may be among these targets since they can be modified by BRCA1/BARD1 in vitro. Here we demonstrate that the BRCA1/BARD1 complex can ubiquitylate both free H2A and H2B histones and histones in the context of nucleosomal particles. We have also investigated the possibility that BRCA1/BARD1 can attach ubiquitin to H2A and H2B residing on the same particle. These results raise the possibility that BRCA1/BARD1 can directly affect nucleosomal structure, dynamics, and function through its ability to modify nucleosomal histones.