Cargando…

BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kalb, Reinhard, Mallery, Donna L., Larkin, Conor, Huang, Jeffrey T.J., Hiom, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382519/
https://www.ncbi.nlm.nih.gov/pubmed/25131202
http://dx.doi.org/10.1016/j.celrep.2014.07.025
_version_ 1782364595485147136
author Kalb, Reinhard
Mallery, Donna L.
Larkin, Conor
Huang, Jeffrey T.J.
Hiom, Kevin
author_facet Kalb, Reinhard
Mallery, Donna L.
Larkin, Conor
Huang, Jeffrey T.J.
Hiom, Kevin
author_sort Kalb, Reinhard
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4382519
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Cell Press
record_format MEDLINE/PubMed
spelling pubmed-43825192015-04-07 BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase Kalb, Reinhard Mallery, Donna L. Larkin, Conor Huang, Jeffrey T.J. Hiom, Kevin Cell Rep Report 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. Cell Press 2014-08-14 /pmc/articles/PMC4382519/ /pubmed/25131202 http://dx.doi.org/10.1016/j.celrep.2014.07.025 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Report
Kalb, Reinhard
Mallery, Donna L.
Larkin, Conor
Huang, Jeffrey T.J.
Hiom, Kevin
BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase
title BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase
title_full BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase
title_fullStr BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase
title_full_unstemmed BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase
title_short BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase
title_sort brca1 is a histone-h2a-specific ubiquitin ligase
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382519/
https://www.ncbi.nlm.nih.gov/pubmed/25131202
http://dx.doi.org/10.1016/j.celrep.2014.07.025
work_keys_str_mv AT kalbreinhard brca1isahistoneh2aspecificubiquitinligase
AT mallerydonnal brca1isahistoneh2aspecificubiquitinligase
AT larkinconor brca1isahistoneh2aspecificubiquitinligase
AT huangjeffreytj brca1isahistoneh2aspecificubiquitinligase
AT hiomkevin brca1isahistoneh2aspecificubiquitinligase