A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase

Ubiquitination of histones plays a critical role in the regulation of several processes within the nucleus, including maintenance of genome stability and transcriptional regulation. The only known ubiquitination site on histones is represented by a conserved Lys residue located at the C terminus of...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Vol. 11; no. 13; pp. 2538 - 2544
Main Authors: Gatti, Marco, Pinato, Sabrina, Maspero, Elena, Soffientini, Paolo, Polo, Simona, Penengo, Lorenza
Format: Journal Article
Language:English
Published: United States Taylor & Francis 01.07.2012
Landes Bioscience
Subjects:
Amino Acid Sequence
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Chromatin Assembly and Disassembly
chromatin remodeling
Cycle
DNA damage response
DNA Repair
DNA-Binding Proteins - metabolism
epigenetics
HEK293 Cells
histone ubiquitination
Histones - chemistry
Histones - genetics
Histones - metabolism
Humans
Landes
Molecular Sequence Data
Mutation
Organogenesis
Protein Structure, Tertiary
Proteins
RNF168 ubiquitin ligase
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
ISSN:1538-4101, 1551-4005, 1551-4005
Online Access:Get full text
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Summary:Ubiquitination of histones plays a critical role in the regulation of several processes within the nucleus, including maintenance of genome stability and transcriptional regulation. The only known ubiquitination site on histones is represented by a conserved Lys residue located at the C terminus of the protein. Here, we describe a novel ubiquitin mark at the N-terminal tail of histone H2As consisting of two Lys residues at positions 13 and 15 (K13/K15). This "bidentate" site is a target of the DNA damage response (DDR) ubiquitin ligases RNF8 and RNF168. Histone mutants lacking the K13/K15 site impair RNF168- and DNA damage-dependent ubiquitination. Conversely, inactivation of the canonical C-terminal site prevents the constitutive monoubiquitination of histone H2As but does not abolish the ubiquitination induced by RNF168. A ubiquitination-defective mutant is obtained by inactivating both the N- and the C-terminal sites, suggesting that these are unique, non-redundant acceptors of ubiquitination on histone H2As. This unprecedented result implies that RNF168 generates a qualitatively different Ub mark on chromatin.
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These authors contributed equally to this work.
ISSN:1538-4101
1551-4005
1551-4005
DOI:10.4161/cc.20919