BRCA1/BARD1 E3 ubiquitin ligase can modify histones H2A and H2B in the nucleosome particle.
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 also be targets in vivo since they can be modified by the BRCA1/BARD1 complex 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. These results raise the possibility that BRCA1/BARD1 can directly affect nucleosomal structure, dynamics, and function through its ability to modify nucleosomal histones.
Thakar
Amit
A
Dept of Molecular Biology University of Wyoming, Laramie, WY 82071, USA.
Parvin
Jeffrey  D
J
Zlatanova
Jordanka
J
D019313:BRCA1 Protein / Q000502:physiology*; D015153:Blotting, Western; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D054875:Ubiquitination
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D006657:Histones; D009707:Nucleosomes; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases