Report

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

Volume 11, Issue 13   July 1, 2012
Pages 2538 - 2544
http://dx.doi.org/10.4161/cc.20919
Keywords: DNA damage response, RNF168 ubiquitin ligase, chromatin remodeling, epigenetics, histone ubiquitination
Authors: Marco Gatti, Sabrina Pinato, Elena Maspero, Paolo Soffientini, Simona Polo and Lorenza Penengo

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Abstract:
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.

Received: May 3, 2012; Accepted: May 29, 2012

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