BRCA1 is a histone-H2A-specific ubiquitin ligase. Kalb, R., Mallery, D. L., Larkin, C., Huang, J. T. J., & Hiom, K. Cell Reports, 8(4):999–1005, August, 2014. doi abstract bibtex 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.
@article{kalb_brca1_2014,
title = {{BRCA1} is a histone-{H2A}-specific ubiquitin ligase},
volume = {8},
issn = {2211-1247},
doi = {10.1016/j.celrep.2014.07.025},
abstract = {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.},
language = {eng},
number = {4},
journal = {Cell Reports},
author = {Kalb, Reinhard and Mallery, Donna L. and Larkin, Conor and Huang, Jeffrey T. J. and Hiom, Kevin},
month = aug,
year = {2014},
keywords = {Amino Acid Sequence, Animals, BRCA1 Protein, Catalytic Domain, Chickens, HEK293 Cells, HeLa Cells, Histones, Humans, Molecular Sequence Data, Nucleosomes, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Ubiquitination, Xenopus laevis},
pages = {999--1005},
}
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