DOI: 10.1093/genetics/148.4.1475. DNA Polymerase Fidelity: From Genetics Toward a Biochemical Understanding

DNA Polymerase Fidelity: From Genetics Toward a Biochemical Understanding

10.1093/genetics/148.4.1475

Crossref journal-article

Oxford University Press (OUP)

Genetics (286)

Abstract

Abstract This review summarizes mutagenesis studies, emphasizing the use of bacteriophage T4 mutator and antimutator strains. Early genetic studies on T4 identified mutator and antimutator variants of DNA polymerase that, in turn, stimulated the development of model systems for the study of DNA polymerase fidelity in vitro. Later enzymatic studies using purified T4 mutator and antimutator polymerases were essential in elucidating mechanisms of base selection and exonuclease proofreading. In both cases, the base analogue 2-aminopurine (2AP) proved tremendously useful—first as a mutagen in vivo and then as a probe of DNA polymerase fidelity in vitro. Investigations into mechanisms of DNA polymerase fidelity inspired theoretical models that, in turn, called for kinetic and thermodynamic analyses. Thus, the field of DNA synthesis fidelity has grown from many directions: genetics, enzymology, kinetics, physical biochemistry, and thermodynamics, and today the interplay continues. The relative contributions of hydrogen bonding and base stacking to the accuracy of DNA synthesis are beginning to be deciphered. For the future, the main challenges lie in understanding the origins of mutational hot and cold spots.

Bibliography

Goodman, M. F., & Fygenson, D. K. (1998). DNA Polymerase Fidelity: From Genetics Toward a Biochemical Understanding. Genetics, 148(4), 1475â1482.

Authors 2

Myron F Goodman (first)
D Kuchnir Fygenson (additional)

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Dates

Type	When
Created	4 years, 6 months ago (Feb. 12, 2021, 6:50 p.m.)
Deposited	3 years, 7 months ago (Jan. 3, 2022, 3:46 a.m.)
Indexed	1 month, 3 weeks ago (July 1, 2025, 6:32 a.m.)
Issued	27 years, 4 months ago (April 1, 1998)
Published	27 years, 4 months ago (April 1, 1998)
Published Online	27 years, 4 months ago (April 1, 1998)
Published Print	27 years, 4 months ago (April 1, 1998)

Funders 0

None

BibTeX

@article{Goodman_1998, title={DNA Polymerase Fidelity: From Genetics Toward a Biochemical Understanding}, volume={148}, ISSN={1943-2631}, url={http://dx.doi.org/10.1093/genetics/148.4.1475}, DOI={10.1093/genetics/148.4.1475}, number={4}, journal={Genetics}, publisher={Oxford University Press (OUP)}, author={Goodman, Myron F and Fygenson, D Kuchnir}, year={1998}, month=apr, pages={1475–1482} }

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