Mirror-Image Thymidine Discriminates against Incorporation of Deoxyribonucleotide Triphosphate into DNA and Repairs Itself by DNA Polymerases,Bioconjugate Chemistry

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Mirror-Image Thymidine Discriminates against Incorporation of Deoxyribonucleotide Triphosphate into DNA and Repairs Itself by DNA Polymerases
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2017-07-26 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00301
Yating Xiao ₁ , Qingju Liu ₁ , Xinjing Tang ₂ , Zhenjun Yang ₂ , Li Wu _{1,

2} , Yujian He _{1,

2}

Affiliation

DNA polymerases are known to recognize preferably d-nucleotides over l-nucleotides during DNA synthesis. Here, we report that several general DNA polymerases catalyze polymerization reactions of nucleotides directed by the DNA template containing an l-thymidine (l-T). The results display that the 5′–3′ primer extension of natural nucleotides get to the end at chiral modification site with Taq and Phanta Max DNA polymerases, but the primer extension proceeds to the end of the template catalyzed by Deep Vent (exo^–), Vent (exo^–), and Therminator DNA polymerases. Furthermore, templating l-nucleoside displays a lag in the deoxyribonucleotide triphosphate (dNTP) incorporation rates relative to natural template by kinetics analysis, and polymerase chain reactions were inhibited with the DNA template containing two or three consecutive l-Ts. Most interestingly, no single base mutation or mismatch mixture corresponding to the location of l-T in the template was found, which is physiologically significant because they provide a theoretical basis on the involvement of DNA polymerase in the effective repair of l-T that may lead to cytotoxicity.

中文翻译：

镜像胸苷区分脱氧核糖核苷酸三磷酸并入DNA并通过DNA聚合酶自行修复

已知DNA聚合酶在DNA合成期间比1-核苷酸优选识别d-核苷酸。在这里，我们报道了几种通用的DNA聚合酶催化由含有1-胸苷（1- T）的DNA模板指导的核苷酸的聚合反应。结果显示，天然核苷酸的5'–3'引物延伸在Taq和Phanta Max DNA聚合酶的手性修饰位点终止，而引物延伸在Deep Vent催化下延伸至模板的末端（exo ^–）。，Vent（exo ^–）和Therminator DNA聚合酶。此外，模板l通过动力学分析，β-核苷相对于天然模板在三磷酸脱氧核糖核苷酸（dNTP）掺入速率方面存在滞后，并且用包含两个或三个连续的1- T的DNA模板抑制了聚合酶链反应。最有趣的是，没有发现对应于模板中l -T位置的单碱基突变或错配混合物，这在生理上很重要，因为它们为DNA聚合酶参与有效修复l -T提供了理论基础。导致细胞毒性。

更新日期：2017-07-28

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