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The RING domain proteins BRCA1 and BARD1 comprise a heterodimeric ubiquitin (E3) ligase that is required for the accumulation of ubiquitin conjugates at sites of DNA damage and for silencing at DNA satellite repeat regions. Despite its links to chromatin, the substrate and underlying function of the BRCA1/BARD1 ubiquitin ligase remain unclear. Here, we show that BRCA1/BARD1 specifically ubiquitylates histone H2A in its C-terminal tail on lysines 127 and 129 in vitro and in vivo. The specificity for K127-129 is acquired only when H2A is within a nucleosomal context. Moreover, site-specific targeting of the BRCA1/BARD1 RING domains to chromatin is sufficient for H2Aub foci formation in vivo. Our data establish BRCA1/BARD1 as a histone-H2A-specific E3 ligase, helping to explain its localization and activities on chromatin in cells.
Pubmed ID: 25131202 RIS Download
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Core facility that provides the following services: NextGen sequencing, Data Analysis. The NextGen Core is a collaboration between the Department of Molecular Biology, the Center for Human Genetics Research, the Center for Computational Biology, and the Executive Committee on Research (ECOR). Currently, the Core operates using a single Ilumina HiSeq instrument, accompanied by Illumina''''s cBot for cluster generation. This upgrade from our Genome Analyzer II doubled our capacity and greatly increased the data amount, quality, and stability over extra-long reads. The Core is located in the state-of-the-art Richard Simches Research Center on Cambridge St. as part of the MGH main campus in Boston. The many multi-investigator groups in the building - including those that study human genetics, stem cells, genomics, and more - make it the perfect location for the Core to service the researchers in those groups. The majority of customers come from MGH, but they also service customers at other academic medical centers and industry.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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