A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure
A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure
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DOI：
10.1038/emboj.2012.104
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发表时间：
2012-05-30
期刊：
影响因子：
11.4
通讯作者：
Dantuma, Nico P.
中科院分区：
文献类型：
--
作者：
Luijsterburg, Martijn S.;Acs, Klara;Dantuma, Nico P.
泛素连接酶RNF 8和RNF 168通过组蛋白H2 A的泛素化和下游修复因子的募集协调DNA损伤信号传导。在这里，我们证明，RNF 8，而不是RNF 168或典型的H2 A泛素连接酶RNF 2，介导广泛的染色质去凝聚。我们的数据表明，CHD 4，催化亚基的NuRD复合物，与RNF 8相互作用，是必不可少的RNF 8介导的染色质展开。CHD 4的染色质重塑活性促进RNF 168和BRCA 1在DNA双链断裂处的有效泛素缀合和组装。有趣的是，RNF 8介导的CHD 4募集和随后的染色质重塑独立于RNF 8的泛素连接酶活性，但涉及与叉头相关（FHA）结构域的非典型相互作用。我们的研究揭示了一种新的染色质重塑辅助泛素化机制，它涉及CHD 4和RNF 8之间的合作，以创造一个局部染色质环境，允许在DNA损伤处组装检查点和修复机制。The EMBO Journal（2012）31，2511-2527. doi：10.1038/daj.2012.104; 2012年4月24日在线发布
The ubiquitin ligases RNF8 and RNF168 orchestrate DNA damage signalling through the ubiquitylation of histone H2A and the recruitment of downstream repair factors. Here, we demonstrate that RNF8, but not RNF168 or the canonical H2A ubiquitin ligase RNF2, mediates extensive chromatin decondensation. Our data show that CHD4, the catalytic subunit of the NuRD complex, interacts with RNF8 and is essential for RNF8-mediated chromatin unfolding. The chromatin remodelling activity of CHD4 promotes efficient ubiquitin conjugation and assembly of RNF168 and BRCA1 at DNA double-strand breaks. Interestingly, RNF8-mediated recruitment of CHD4 and subsequent chromatin remodelling were independent of the ubiquitin-ligase activity of RNF8, but involved a non-canonical interaction with the forkhead-associated (FHA) domain. Our study reveals a new mechanism of chromatin remodelling-assisted ubiquitylation, which involves the cooperation between CHD4 and RNF8 to create a local chromatin environment that is permissive to the assembly of checkpoint and repair machineries at DNA lesions. The EMBO Journal (2012) 31, 2511-2527. doi: 10.1038/emboj.2012.104; Published online 24 April 2012