A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase.
A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase.
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DOI：
10.4161/cc.20919
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发表时间：
2012-07-01
期刊：
影响因子：
--
通讯作者：
Penengo L
中科院分区：
文献类型：
--
作者：
Gatti M;Pinato S;Maspero E;Soffientini P;Polo S;Penengo L
组蛋白的泛素化在调节细胞核内的几个过程中起着关键作用，包括维持基因组稳定性和转录调节。组蛋白上唯一已知的泛素化位点是位于蛋白质C末端的保守的赖氨酸残基。在这里，我们描述了一种新的泛素标记在N-末端尾部的组蛋白H2 As组成的两个赖氨酸残基在位置13和15（K13/K15）。这个“双齿”位点是DNA损伤反应（DDR）遍在蛋白连接酶RNF 8和RNF 168的靶点。缺乏K13/K15位点的组蛋白突变体损害RNF 168和DNA损伤依赖的泛素化。相反，典型的C-末端位点的失活阻止了组蛋白H2 As的组成性单泛素化，但并没有消除由RNF 168诱导的泛素化。一个泛素化缺陷的突变体是通过失活的N-和C-末端位点，这表明这些是独特的，非冗余的组蛋白H2 As上的泛素化受体。这一前所未有的结果意味着RNF 168在染色质上产生了一个性质不同的Ub标记。
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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影响因子：
5.3
作者：
Pinato, Sabrina;Gatti, Marco;Penengo, Lorenza
通讯作者：
Penengo, Lorenza
影响因子：
16
作者：
Sims, Joshua J.;Cohen, Robert E.
通讯作者：
Cohen, Robert E.
影响因子：
14.8
作者：
Rappsilber, Juri;Mann, Matthias;Ishihama, Yasushi
通讯作者：
Ishihama, Yasushi
影响因子：
56.9
作者：
Wang, Bin;Matsuoka, Shuhei;Elledge, Stephen J.
通讯作者：
Elledge, Stephen J.
影响因子：
64.5
作者：
Penengo, L;Mapelli, M;Schneider, TR
通讯作者：
Schneider, TR