Cited by 142DNA and Nucleic Acid ChemistryProtein Structure and DynamicsChemical Reaction Mechanisms

A Reexamination of the Nucleotide Incorporation Fidelity of DNA Polymerases

Showalter, Alexander K., Tsai, Ming-Daw·2002·Biochemistry

Abstract

Intensive study has been devoted to understanding the kinetic and structural bases underlying the exceptionally high fidelity (low error frequencies) of the typical DNA polymerase. Commonly proposed explanations have included (i) the concept of fidelity check points, in which the correctness of a nascent base pair match is tested at multiple points along the reaction pathway, and (ii) an induced-fit fidelity enhancement mechanism based on a rate-limiting, substrate-induced conformational change. In this article, we consider the evidence and theoretical framework for the involvement of such mechanisms in fidelity enhancement. We suggest that a "simplified" model, in which fidelity is derived fundamentally from differential substrate binding at the transition state of a rate-limiting chemical step, is consistent with known data and sufficient to explain the substrate selectivity of these enzymes.

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Crossref · 10.1021/bi026021i

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  • Kinetic studies have established that fidelity depends on differences in the binding affinities and insertion rates of incorrect versus correct dNTPs.

    “Kinetic studies (reviewed in Refs.15,19,[33][34][35][36] have established that fidelity depends on differences in the binding affinities and insertion rates of incorrect versus correct dNTPs.”

    From DNA Replication Fidelity (2004) · cites this paper as [35]

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Authors
Showalter, A. K., & Tsai, M.-D.
Affiliations
The Ohio State University (US)
Venue
Biochemistry
Published
2002-08-01
Volume
41
Issue
34
Pages
10571-10576
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
OpenAlex
W2114997522
Cited by
142
References
40
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 7 · 2013: 2 · 2012: 4
FWCI
0.80
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM 43268, R01GM043268)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
Keywords
DNA polymerase, induced fit, substrate binding, transition state, rate-determining step, substrate specificity, error rate, conformational change
MeSH terms
DNA-Directed DNA Polymerase, DNA Replication, Kinetics, Models, Biological, Nucleotides, Protein Binding, Protein Conformation, Substrate Specificity, Thermodynamics

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