Roles of mutagenic translesion synthesis in mammalian genome stability, health and disease
Roles of mutagenic translesion synthesis in mammalian genome stability, health and disease
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DOI：
10.1016/j.dnarep.2015.01.001
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发表时间：
2015-05-01
期刊：
影响因子：
3.8
通讯作者：
de Wind, Niels
中科院分区：
文献类型：
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作者：
Jansen, Jacob G.;Tsaalbi-Shtylik, Anastasia;de Wind, Niels
真核生物中大多数自发的和 DNA 损伤诱导的核苷酸取代依赖于跨损伤合成聚合酶 Rev1 和 Pol zeta，后者由催化亚基 Rev3 和辅助蛋白 Rev7 组成。在这里，我们回顾 Rev1/Pol zeta 依赖性跨损伤合成的调节、生化和细胞功能。这些与具有 Rev1、Rev3 或 Rev7 缺陷的小鼠模型的表型相关。数据表明 Rev1/Pol zeta 介导的跨损伤合成对于适应性免疫很重要，同时在肿瘤发生中发挥着矛盾的作用。另一方面，通过实现内源性受损模板的复制，Rev1/Pol zeta 依赖性跨损伤合成可以保护干细胞，从而防止衰老特征。总之，DNA 螺旋扭曲核苷酸损伤处的 Rev1/Pol zeta 依赖性跨损伤合成协调了决定机体健康和疾病的多效性反应。 (C) 2015 Elsevier B.V. 保留所有权利。
Most spontaneous and DNA damage-induced nucleotide substitutions in eukaryotes depend on translesion synthesis polymerases Rev1 and Pol zeta, the latter consisting of the catalytic subunit Rev3 and the accessory protein Rev7. Here we review the regulation, and the biochemical and cellular functions, of Rev1/Pol zeta-dependent translesion synthesis. These are correlated with phenotypes of mouse models with defects in Rev1, Rev3 or Rev7. The data indicate that Rev1/Pol zeta-mediated translesion synthesis is important for adaptive immunity while playing paradoxical roles in oncogenesis. On the other hand, by enabling the replication of endogenously damaged templates, Rev1/Pol zeta-dependent translesion synthesis protects stem cells, thereby preventing features of ageing. In conclusion, Rev1/Pol zeta-dependent translesion synthesis at DNA helix-distorting nucleotide lesions orchestrates pleiotropic responses that determine organismal fitness and disease. (C) 2015 Elsevier B.V. All rights reserved.