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Mechanisms of mutagenesis: DNA replication in the presence of DNA damage.
Mutation Research/Reviews in Mutation Research ( IF 5.3 ) Pub Date : 2016-05-29 , DOI: 10.1016/j.mrrev.2016.03.006
Binyan Liu 1 , Qizhen Xue 1 , Yong Tang 1 , Jia Cao 1 , F Peter Guengerich 2 , Huidong Zhang 1
Affiliation  

Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, Escherichia coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis.

中文翻译:

诱变的机制:在DNA损伤的情况下进行DNA复制。

环境诱变剂会导致DNA损伤,从而干扰复制并产生突变,从而导致癌症和其他疾病。我们讨论了由DNA破坏引起的诱变机制,从单个聚合酶的DNA复制水平到一些典型模型生物(包括噬菌体T7,T4,Sulfolobus solfataricus,大肠杆菌,酵母和人)的复杂DNA复制体。对于单个DNA聚合酶,DNA损伤可通过三种主要方式影响复制:降低复制保真度,导致移码突变和阻止复制。对于DNA复制体,即使使用单个DNA聚合酶,蛋白质相互作用和辅助蛋白质的功能也可以产生截然不同的结果。DNA复制体在复制过程中发生突变的机制是一个长期存在的问题。使用新的方法和技术,现在可以就绕过DNA损伤的方式研究某些生物体和人类细胞提取物的复制体。在这篇综述中,我们考虑了在单个DNA聚合酶和复杂DNA复制体(包括跨病变DNA合成)水平上复制过程中DNA损伤引起的诱变的分子机制。
更新日期:2019-11-01
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