Cited by 75DNA Repair MechanismsDNA and Nucleic Acid ChemistryRNA and protein synthesis mechanisms

Requirement of Watson-Crick Hydrogen Bonding for DNA Synthesis by Yeast DNA Polymerase η

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Washington, M. Todd, Helquist, Sandra A., Kool, Eric T., Prakash, Louise, Prakash, Satya·2003·Molecular and Cellular Biology

Abstract

Classical high-fidelity DNA polymerases discriminate between the correct and incorrect nucleotides by using geometric constraints imposed by the tight fit of the active site with the incipient base pair. Consequently, Watson-Crick (W-C) hydrogen bonding between the bases is not required for the efficiency and accuracy of DNA synthesis by these polymerases. DNA polymerase eta (Poleta) is a low-fidelity enzyme able to replicate through DNA lesions. Using difluorotoluene, a nonpolar isosteric analog of thymine unable to form W-C hydrogen bonds with adenine, we found that the efficiency and accuracy of nucleotide incorporation by Poleta are severely impaired. From these observations, we suggest that W-C hydrogen bonding is required for DNA synthesis by Poleta; in this regard, Poleta differs strikingly from classical high-fidelity DNA polymerases.

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Crossref · 10.1128/mcb.23.14.5107-5112.2003

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  • These ideas are supported by structural information and by a report that the insertion fidelity of yeast Pol η is severely impaired with difluorotoluene, a nonpolar isosteric analog of thymine that is unable to form Watson-Crick hydrogen bonds with adenine.

    “These ideas are supported by structural information (20, 21, 26 -28) and by a report (29) that the insertion fidelity of yeast Pol ␩ is severely impaired with difluorotoluene, a nonpolar isosteric analog of thymine that is unable to form Watson-Crick hydrogen bonds with adenine.”

    From DNA Replication Fidelity (2004) · cites this paper as [29]

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Authors
Washington, M. T., Helquist, S. A., Kool, E. T., Prakash, L., & Prakash, S.
Affiliations
  • The University of Texas Medical Branch at Galveston (US)
  • Stanford University (US)
Corresponding author
Prakash, Satya
Venue
Molecular and Cellular Biology
Published
2003-07-01
Volume
23
Issue
14
Pages
5107-5112
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2111754594
Cited by
75
References
51
Citations by year
2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 5
FWCI
2.53
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01gm019261-30)
  • National Institute of General Medical Sciences (GM-19261, GM52956, R01GM052956)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
DNA polymerase eta, Watson-Crick hydrogen bonding, nucleotide incorporation, base pair geometry, yeast
MeSH terms
Y-Family DNA Polymerases, DNA, DNA-Directed DNA Polymerase, Fungal Proteins, Hydrogen Bonding, Kinetics, Nucleotides, Toluene, Yeasts

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