BRCA1/BARD1 E3 Ubiquitin Ligase Can Modify Histones H2A and H2B in the Nucleosome Particle

摘要

BRCAl, the protein product of the Breast Cancer Susceptibility Gene {BRCAl) has been implicated in multiple pathways that preserve genome stability, including cell cycle control, DNA repair, transcription, and chromatin remodeling. BRCAl, 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 also be targets in vivo since they can be modified by the BRCA1/BARD1 complex in vitro. Here we demonstrate that the BRCAl/BARD1 complex can ubiquitylate both free H2A and H2B histones and histones in the context of nucleosomal particles. These results raise the possibility that BRCAl/ BARD1 can directly affect nucleosomal structure, dynamics, and function through its ability to modify nucleosomal histones.