Chem Res Toxicol. 2021 Mar 15;34(3):695-698. doi: 10.1021/acs.chemrestox.0c00478. Epub 2021 Jan 8.
Alkylation represents a main form of DNA damage. The position of guanine is frequently alkylated in DNA. The SOS-induced polymerases have been shown to be capable of bypassing various DNA damage products in . Herein, we explored the influences of four -alkyl-dG lesions (alkyl = ethyl, -butyl, isobutyl, or -butyl) on DNA replication in AB1157 cells and the corresponding strains with polymerases (Pol) II, IV, and V being individually or simultaneously knocked out. We found that -Et-dG is slightly less blocking to DNA replication than the -Bu-dG lesions, which display very similar replication bypass efficiencies. Additionally, Pol II and, to a lesser degree, Pol IV and Pol V are required for the efficient bypass of the -alkyl-dG adducts, and none of these lesions was mutagenic. Together, our results support that the efficient replication across small -alkyl-dG DNA adducts in depends mainly on Pol II.
烷基化是 DNA 损伤的主要形式之一。鸟嘌呤在 DNA 中经常被烷基化。已经表明，SOS 诱导的聚合酶能够在体内绕过各种 DNA 损伤产物。在此，我们研究了四种 -烷基-dG 损伤（烷基=乙基、-丁基、异丁基或-丁基）对 AB1157 细胞中 DNA 复制的影响，以及相应的聚合酶（Pol）II、IV 和 V 被单独或同时敲除的菌株。我们发现 -Et-dG 对 DNA 复制的阻断作用略小于 -Bu-dG 损伤，而后者显示出非常相似的复制绕过效率。此外，Pol II，以及程度较小的 Pol IV 和 Pol V，对于有效绕过 -烷基-dG 加合物是必需的，而这些损伤都没有致突变性。综上所述，我们的结果表明，在体内有效复制小的 -烷基-dG DNA 加合物主要依赖于 Pol II。
