Cockayne syndrome B protein regulates recruitment of the Elongin A ubiquitin ligase to sites of DNA damage.
Cockayne syndrome B protein regulates recruitment of the Elongin A ubiquitin ligase to sites of DNA damage.
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DOI：
10.1074/jbc.c117.777946
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发表时间：
2017-04-21
期刊：
影响因子：
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通讯作者：
Conaway RC
中科院分区：
文献类型：
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作者：
Weems JC;Slaughter BD;Unruh JR;Boeing S;Hall SM;McLaird MB;Yasukawa T;Aso T;Svejstrup JQ;Conaway JW;Conaway RC
延伸蛋白A作为RNA聚合酶II（Pol II）延伸因子延伸蛋白的转录活性亚基和作为Cullin-RING E3泛素连接酶的底物识别亚基执行双重功能，所述Cullin-RING E3泛素连接酶响应于DNA损伤而使Pol II泛素化。延伸蛋白A泛素连接酶的组装及其在DNA损伤位点的募集是一个由DNA损伤剂和α-鹅膏蕈碱（一种诱导Pol II停滞的药物）诱导的严格调控的过程。在这项研究中，我们证明了（i）延伸蛋白A和泛素连接酶亚基CUL 5在细胞中与Cockayne综合征B（CS B）蛋白相关，（ii）这种相互作用也由DNA损伤剂和α-鹅膏蕈碱诱导。此外，我们提出的证据表明，CSB蛋白促进稳定的招聘的延伸蛋白A泛素连接酶的DNA损伤的网站。我们的研究结果是一致的模型，延伸蛋白A泛素连接酶和CSB蛋白功能在一个共同的途径，以响应Pol II失速和DNA损伤。
Elongin A performs dual functions as the transcriptionally active subunit of RNA polymerase II (Pol II) elongation factor Elongin and as the substrate recognition subunit of a Cullin-RING E3 ubiquitin ligase that ubiquitylates Pol II in response to DNA damage. Assembly of the Elongin A ubiquitin ligase and its recruitment to sites of DNA damage is a tightly regulated process induced by DNA-damaging agents and α-amanitin, a drug that induces Pol II stalling. In this study, we demonstrate (i) that Elongin A and the ubiquitin ligase subunit CUL5 associate in cells with the Cockayne syndrome B (CSB) protein and (ii) that this interaction is also induced by DNA-damaging agents and α-amanitin. In addition, we present evidence that the CSB protein promotes stable recruitment of the Elongin A ubiquitin ligase to sites of DNA damage. Our findings are consistent with the model that the Elongin A ubiquitin ligase and the CSB protein function together in a common pathway in response to Pol II stalling and DNA damage.