Proofreading of DNA polymerase: a new kinetic model with higher-order terminal effects

doi:http://dx.doi.org/10.1088/0953-8984/29/2/025101

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	Proofreading of DNA polymerase: a new kinetic model with higher-order terminal effects
	Ou-Yang, ZC; Song, YS; Shu, YG; Zhou, X; Li, M; Li, M (reprint author), Univ Chinese Acad Sci, Sch Phys Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China.
刊名	JOURNAL OF PHYSICS-CONDENSED MATTER
	2017
卷号	29 期号:2 页码:25101
关键词	Dna Polymerase Proofreading Kinetics Fidelity Higher-order Terminal Effects
DOI	http://dx.doi.org/10.1088/0953-8984/29/2/025101
英文摘要	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.
学科主题	Physics
语种	英语
内容类型	期刊论文
源URL	[http://ir.itp.ac.cn/handle/311006/22149]
专题	理论物理研究所_理论物理所1978-2010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.
推荐引用方式 GB/T 7714	Ou-Yang, ZC,Song, YS,Shu, YG,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	Ou-Yang, ZC,Song, YS,Shu, YG,Zhou, X,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	Ou-Yang, ZC,et al."Proofreading of DNA polymerase: a new kinetic model with higher-order terminal effects".JOURNAL OF PHYSICS-CONDENSED MATTER 29.2(2017):25101.