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Influence of DNA Lesions on Polymerase-Mediated DNA Replication at Single-Molecule Resolution
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2017-10-23 00:00:00 , DOI: 10.1021/acs.chemrestox.7b00224
Hailey L Gahlon 1, 2 , Louis J Romano 3 , David Rueda 1, 2
Affiliation  

Faithful replication of DNA is a critical aspect in maintaining genome integrity. DNA polymerases are responsible for replicating DNA, and high-fidelity polymerases do this rapidly and at low error rates. Upon exposure to exogenous or endogenous substances, DNA can become damaged and this can alter the speed and fidelity of a DNA polymerase. In this instance, DNA polymerases are confronted with an obstacle that can result in genomic instability during replication, for example, by nucleotide misinsertion or replication fork collapse. It is important to know how DNA polymerases respond to damaged DNA substrates to understand the mechanism of mutagenesis and chemical carcinogenesis. Single-molecule techniques have helped to improve our current understanding of DNA polymerase-mediated DNA replication, as they enable the dissection of mechanistic details that can otherwise be lost in ensemble-averaged experiments. These techniques have also been used to gain a deeper understanding of how single DNA polymerases behave at the site of the damage in a DNA substrate. In this review, we evaluate single-molecule studies that have examined the interaction between DNA polymerases and damaged sites on a DNA template.

中文翻译:

DNA 损伤对单分子分辨率下聚合酶介导的 DNA 复制的影响

DNA 的忠实复制是维持基因组完整性的一个关键方面。DNA 聚合酶负责复制 DNA,而高保真聚合酶可以快速且低错误率地完成此任务。暴露于外源性或​​内源性物质后,DNA 会受损,这会改变 DNA 聚合酶的速度和保真度。在这种情况下,DNA 聚合酶面临着可能导致复制过程中基因组不稳定的障碍,例如,核苷酸错误插入或复制叉折叠。了解 DNA 聚合酶如何响应受损的 DNA 底物以了解诱变和化学致癌作用的机制非常重要。单分子技术有助于提高我们目前对 DNA 聚合酶介导的 DNA 复制的理解,因为它们能够剖析机械细节,否则这些细节可能会在整体平均实验中丢失。这些技术也被用来更深入地了解单个 DNA 聚合酶在 DNA 底物损伤部位的行为。在这篇综述中,我们评估了单分子研究,这些研究检查了 DNA 聚合酶与 DNA 模板上受损位点之间的相互作用。
更新日期:2017-10-23
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