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Mechanisms of mutagenesis induced by DNA lesions: multiple factors affect mutations in translesion DNA synthesis.
Critical Reviews in Biochemistry and Molecular Biology ( IF 6.5 ) Pub Date : 2020-05-24 , DOI: 10.1080/10409238.2020.1768205
Huidong Zhang 1
Affiliation  

Environmental mutagens lead to mutagenesis. However, the mechanisms are very complicated and not fully understood. Environmental mutagens produce various DNA lesions, including base-damaged or sugar-modified DNA lesions, as well as epigenetically modified DNA. DNA polymerases produce mutation spectra in translesion DNA synthesis (TLS) through misincorporation of incorrect nucleotides, frameshift deletions, blockage of DNA replication, imbalance of leading- and lagging-strand DNA synthesis, and genome instability. Motif or subunit in DNA polymerases further affects the mutations in TLS. Moreover, protein interactions and accessory proteins in DNA replisome also alter mutations in TLS, demonstrated by several representative DNA replisomes. Finally, in cells, multiple DNA polymerases or cellular proteins collaborate in TLS and reduce in vivo mutagenesis. Summaries and perspectives were listed. This review shows mechanisms of mutagenesis induced by DNA lesions and the effects of multiple factors on mutations in TLS in vitro and in vivo.



中文翻译:

DNA损伤诱导诱变的机制:多种因素影响跨病变DNA合成的突变。

环境诱变剂导致诱变。但是,机制非常复杂,尚未完全理解。环境诱变剂会产生各种DNA损伤,包括碱基损坏或糖修饰的DNA损伤以及表观遗传修饰的DNA。DNA聚合酶通过错误核苷酸的错误掺入,移码缺失,DNA复制的阻滞,前链和后链DNA合成的不平衡以及基因组的不稳定性,在跨病变DNA合成(TLS)中产生突变谱。DNA聚合酶中的基序或亚基进一步影响TLS中的突变。而且,DNA复制体中的蛋白质相互作用和辅助蛋白质也会改变TLS中的突变,这由几个代表性的DNA复制体所证明。最后,在细胞中,多种DNA聚合酶或细胞蛋白在TLS中协同作用并减少体内诱变。列出了摘要和观点。这篇综述显示了由DNA损伤诱导的诱变的机制和多种因素对TLS突变的影响在体外体内

更新日期:2020-05-24
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