RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response
RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response
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DOI：
10.1002/embr.201338369
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发表时间：
2014-05-01
期刊：
影响因子：
7.7
通讯作者：
Boddy, Michael N.
中科院分区：
文献类型：
--
作者：
Groocock, Lynda M.;Nie, Minghua;Boddy, Michael N.
泛素和小泛素样修饰物（SUMO）对DNA修复和检查点蛋白的翻译后修饰决定了DNA损伤反应（DDR）。泛素连接酶RNF4通过选择性识别和泛素化SUMO修饰的蛋白质，整合SUMO和泛素信号。在这里，我们定义了一个关键的新的决定因素的目标歧视RNF4，除了相互作用与相扑。我们在RNF4 RING结构域中鉴定了一个核小体靶向基序，该基序可以结合DNA，从而使RNF4能够选择性地泛素化核小体组蛋白。此外，RNF4核小体靶向对于通过53BP1介导的非同源末端连接修复TRF2缺失的功能失调的端粒是至关重要的。
The post-translational modification of DNA repair and checkpoint proteins by ubiquitin and small ubiquitin-like modifier (SUMO) critically orchestrates the DNA damage response (DDR). The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin, through its selective recognition and ubiquitination of SUMO-modified proteins. Here, we define a key new determinant for target discrimination by RNF4, in addition to interaction with SUMO. We identify a nucleosome-targeting motif within the RNF4 RING domain that can bind DNA and thereby enables RNF4 to selectively ubiquitinate nucleosomal histones. Furthermore, RNF4 nucleosome-targeting is crucially required for the repair of TRF2-depleted dysfunctional telomeres by 53BP1-mediated non-homologous end joining.