Control of DNA Damage Bypass by Ubiquitylation of PCNA
Control of DNA Damage Bypass by Ubiquitylation of PCNA
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DOI：
10.3390/genes11020138
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发表时间：
2020-01
期刊：
影响因子：
3.5
通讯作者：
B. Ripley;M. Gildenberg;M. Washington
中科院分区：
文献类型：
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作者：
B. Ripley;M. Gildenberg;M. Washington
DNA损伤通过干扰DNA复制而导致基因组不稳定。细胞有几个损伤旁路，可以减轻复制过程中DNA损伤的影响。这些途径包括跨损伤合成和模板切换。这些途径主要是通过对增殖细胞核抗原(增殖细胞核抗原)的翻译后修饰来调节的，增殖细胞核抗原是一种重要的复制辅助因子。增殖细胞核抗原的单一泛素化促进跨损伤合成，K63连接的多泛素化促进模板切换。本文将从结构和生化角度讨论这些翻译后修饰的增殖细胞核抗原如何控制这些旁路通路的机制。我们将重点介绍促进增殖细胞核抗原单泛素化和多泛素化的E3泛素连接酶Rad18和Rad5的结构和功能。最后，我们回顾了关于增殖细胞核抗原的翻译后修饰如何调节促进损伤旁路的多蛋白复合体的组装的替代想法。
DNA damage leads to genome instability by interfering with DNA replication. Cells possess several damage bypass pathways that mitigate the effects of DNA damage during replication. These pathways include translesion synthesis and template switching. These pathways are regulated largely through post-translational modifications of proliferating cell nuclear antigen (PCNA), an essential replication accessory factor. Mono-ubiquitylation of PCNA promotes translesion synthesis, and K63-linked poly-ubiquitylation promotes template switching. This article will discuss the mechanisms of how these post-translational modifications of PCNA control these bypass pathways from a structural and biochemical perspective. We will focus on the structure and function of the E3 ubiquitin ligases Rad18 and Rad5 that facilitate the mono-ubiquitylation and poly-ubiquitylation of PCNA, respectively. We conclude by reviewing alternative ideas about how these post-translational modifications of PCNA regulate the assembly of the multi-protein complexes that promote damage bypass pathways.