ITP OpenIR  > 理论物理所2017年知识产出
Proofreading of DNA polymerase: a new kinetic model with higher-order terminal effects
Song, YS; Shu, YG; Zhou, X; Ou-Yang, ZC; Li, M; Li, M (reprint author), Univ Chinese Acad Sci, Sch Phys Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China.
2017
发表期刊JOURNAL OF PHYSICS-CONDENSED MATTER
卷号29期号:2页码:25101
文章类型Article
摘要The fidelity of DNA replication by DNA polymerase (DNAP) has long been an important issue in biology. While numerous experiments have revealed details of the molecular structure and working mechanism of DNAP which consists of both a polymerase site and an exonuclease (proofreading) site, there were quite a few theoretical studies on the fidelity issue. The first model which explicitly considered both sites was proposed in the 1970s and the basic idea was widely accepted by later models. However, all these models did not systematically investigate the dominant factor on DNAP fidelity, i.e. the higher-order terminal effects through which the polymerization pathway and the proofreading pathway coordinate to achieve high fidelity. In this paper, we propose a new and comprehensive kinetic model of DNAP based on some recent experimental observations, which includes previous models as special cases. We present a rigorous and unified treatment of the corresponding steady-state kinetic equations of any-order terminal effects, and derive analytical expressions for fidelity in terms of kinetic parameters under bio-relevant conditions. These expressions offer new insights on how the higher-order terminal effects contribute substantially to the fidelity in an order-by-order way, and also show that the polymerization-and-proofreading mechanism is dominated only by very few key parameters. We then apply these results to calculate the fidelity of some real DNAPs, which are in good agreements with previous intuitive estimates given by experimentalists.
关键词Dna Polymerase Proofreading Kinetics Fidelity Higher-order Terminal Effects
学科领域Physics
资助者National Basic Research Program of China (973 program) [2013CB932804] ; National Basic Research Program of China (973 program) [2013CB932804] ; National Natural Science Foundation of China [11105218, 91027046, 11574329, 11322543, 11675180] ; National Natural Science Foundation of China [11105218, 91027046, 11574329, 11322543, 11675180] ; National Basic Research Program of China (973 program) [2013CB932804] ; National Basic Research Program of China (973 program) [2013CB932804] ; National Natural Science Foundation of China [11105218, 91027046, 11574329, 11322543, 11675180] ; National Natural Science Foundation of China [11105218, 91027046, 11574329, 11322543, 11675180]
DOIhttp://dx.doi.org/10.1088/0953-8984/29/2/025101
关键词[WOS]REPLICATION FIDELITY ; ESCHERICHIA-COLI ; CRYSTAL-STRUCTURE ; STEADY-STATE ; I KLENOW ; III HOLOENZYME ; ACTIVE-SITE ; MECHANISM ; EXONUCLEASE ; DYNAMICS
语种英语
资助者National Basic Research Program of China (973 program) [2013CB932804] ; National Basic Research Program of China (973 program) [2013CB932804] ; National Natural Science Foundation of China [11105218, 91027046, 11574329, 11322543, 11675180] ; National Natural Science Foundation of China [11105218, 91027046, 11574329, 11322543, 11675180] ; National Basic Research Program of China (973 program) [2013CB932804] ; National Basic Research Program of China (973 program) [2013CB932804] ; National Natural Science Foundation of China [11105218, 91027046, 11574329, 11322543, 11675180] ; National Natural Science Foundation of China [11105218, 91027046, 11574329, 11322543, 11675180]
WOS类目Physics, Condensed Matter
引用统计
文献类型期刊论文
条目标识符http://ir.itp.ac.cn/handle/311006/22149
专题理论物理所2017年知识产出
通讯作者Li, M (reprint author), Univ Chinese Acad Sci, Sch Phys Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China.
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GB/T 7714
Song, YS,Shu, YG,Zhou, X,et al. Proofreading of DNA polymerase: a new kinetic model with higher-order terminal effects[J]. JOURNAL OF PHYSICS-CONDENSED MATTER,2017,29(2):25101.
APA Song, YS,Shu, YG,Zhou, X,Ou-Yang, ZC,Li, M,&Li, M .(2017).Proofreading of DNA polymerase: a new kinetic model with higher-order terminal effects.JOURNAL OF PHYSICS-CONDENSED MATTER,29(2),25101.
MLA Song, YS,et al."Proofreading of DNA polymerase: a new kinetic model with higher-order terminal effects".JOURNAL OF PHYSICS-CONDENSED MATTER 29.2(2017):25101.
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