UV-DDB ubiquitinates XPC

The role of UV-DDB-mediated ubiquitination in global genome nucleotide excision repair (GG-NER) has not been fully elucidated.<p>In the absence of DNA damage, the ubiquitin ligase activity of UV-DDB complex is inhibited by association with the COP9 signalosome (CSN complex), which dissociates from the UV-DDB complex upon binding to damaged DNA (Groisman et al. 2003, Fischer et al. 2011). Ubiquitination of XPC by UV-DDB promotes XPC retention at GG-NER sites, while progressive autoubiquitination of UV-DDB promotes the dissociation of UV-DDB from the DNA and may act as an intracellular signal (Sugasawa et al. 2005). The UV-DDB complex also ubiquitinates histones H2A, H3 and H4, which may trigger chromatin remodeling at DNA damage site and regulate the accessibility of damaged DNA to repair factors (Kapetanaki et al. 2006, Wang et al. 2006).

紫外线-DDB介导的泛素化在全局基因组核苷酸切除修复（GG-NER）中的作用尚未得到充分阐明。<p>在缺乏DNA损伤的情况下，紫外线-DDB复合物的泛素连接酶活性受到与COP9信号osome（CSN复合物）的结合所抑制，该复合物在结合受损DNA后从紫外线-DDB复合物中解离（Groisman等，2003年，Fischer等，2011年）。紫外线-DDB对XPC的泛素化促进XPC在GG-NER位点的滞留，而UV-DDB的渐进式自泛素化则促进UV-DDB从DNA中解离，并可能作为一种细胞内信号（Sugasawa等，2005年）。此外，UV-DDB复合物还能泛素化组蛋白H2A、H3和H4，这可能会触发DNA损伤位点的染色质重塑，并调节受损DNA对修复因子的可及性（Kapetanaki等，2006年，Wang等，2006年）。