Replicative bypass studies of l-deoxyribonucleosides in Vitro and in E. coli cell

Author:

Kan Yuhe,Jin Zhaoyang,Ke Yongqi,Lin Dao,Yan Liang,Wu Li,He Yujian

Abstract

Abstractl-nucleosides were the most important antiviral lead compounds because they can inhibit viral DNA polymerase and DNA synthesis of many viruses, whereas they may lead to mutations in DNA replication and cause genomic instability. In this study, we reported the replicative bypass of l-deoxynucleosides in recombinant DNA by restriction enzyme–mediated assays to examine their impact on DNA replication in vitro and in E. coli cells. The results showed that a template l-dC inhibited Taq DNA polymerase reaction, whereas it can be bypassed by Vent (exo-) DNA polymerase as well as in cell replication, inserting correct nucleotides opposite l-dC. l-dG can be bypassed by Taq DNA polymerase and in E. coli cells, maintaining insertion of correct incoming nucleotides, and l-dG induced mutagenic replication by Vent (exo-) DNA polymerase. In contrast, l-dA can induced mutagenic replication in vitro and in E. coli cells. MD simulations were performed to investigate how DNA polymerase affected replicative bypass and mutations when d-nucleosides replaced with l-nucleosides. This study will provide a basis for the ability to assess the cytotoxic and mutagenic properties of the l-nucleoside drugs.

Funder

Highlevel introduction of talent research start-up fund in Inner Mongolia University Funding Project

Beijing Natural Science Foundation

National Natural Science Foundation of China

State Key Laboratory of Natural and Biomimetic Drugs

Fundamental Research Funds for the Central Universities

National Key Research and Development Program of China

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3