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PMID: 24518117 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The nucleosome acidic patch plays a critical role in RNF168-dependent ubiquitination of histone H2A.

Nature communications ·Vol. 5 ·2014-00-00 ·Pages 3291

Mattiroli F, Uckelmann M, Sahtoe DD, van Dijk WJ, Sixma TK

Abstract

During DNA damage response, the RING E3 ligase RNF168 ubiquitinates nucleosomal H2A at K13-15. Here we show that the ubiquitination reaction is regulated by its substrate. We define a region on the RING domain important for target recognition and identify the H2A/H2B dimer as the minimal substrate to confer lysine specificity to the RNF168 reaction. Importantly, we find an active role for the substrate in the reaction. H2A/H2B dimers and nucleosomes enhance the E3-mediated discharge of ubiquitin from the E2 and redirect the reaction towards the relevant target, in a process that depends on an intact acidic patch. This active contribution of a region distal from the target lysine provides regulation of the specific K13-15 ubiquitination reaction during the complex signalling process at DNA damage sites.

MeSH Terms
HEK293 Cells Histones/metabolism Humans Nucleosomes/metabolism Ubiquitin-Protein Ligases/metabolism Ubiquitination
Chemicals
Histones Nucleosomes RNF168 protein, human Ubiquitin-Protein Ligases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mattiroli Francesca
1] Division of Biochemistry and Center for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands [2] [3].
Uckelmann Michael
1] Division of Biochemistry and Center for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands [2].
Sahtoe Danny D
Division of Biochemistry and Center for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
van Dijk Willem J
Division of Biochemistry and Center for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Sixma Titia K
Division of Biochemistry and Center for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms4291
Published
2014-00-00
Pages
3291
Language
English
Region
England
NLM ID
101528555
PMCID
PMC3929782
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1038/ncomms4291 PMC Full Text View journal details
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