Cited by 200DNA Repair MechanismsDNA and Nucleic Acid ChemistryBiochemical and Molecular Research

Preferential Incorporation of G Opposite Template T by the Low-Fidelity Human DNA Polymerase ι

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Zhang, Yanbin, Yuan, Fenghua, Wu, Xiaohua, Wang, Zhigang·2000·Molecular and Cellular Biology

Abstract

DNA polymerase activity is essential for replication, recombination, repair, and mutagenesis. All DNA polymerases studied so far from any biological source synthesize DNA by the Watson-Crick base-pairing rule, incorporating A, G, C, and T opposite the templates T, C, G, and A, respectively. Non-Watson-Crick base pairs would lead to mutations. In this report, we describe the ninth human DNA polymerase, Pol(iota), encoded by the RAD30B gene. We show that human Pol(iota) violates the Watson-Crick base-pairing rule opposite template T. During base selection, human Pol(iota) preferred T-G base pairing, leading to G incorporation opposite template T. The resulting T-G base pair was less efficiently extended by human Pol(iota) compared to the Watson-Crick base pairs. Consequently, DNA synthesis frequently aborted opposite template T, a property we designated the T stop. This T stop restricted human Pol(iota) to a very short stretch of DNA synthesis. Furthermore, kinetic analyses show that human Pol(iota) copies template C with extraordinarily low fidelity, misincorporating T, A, and C with unprecedented frequencies of 1/9, 1/10, and 1/11, respectively. Human Pol(iota) incorporated one nucleotide opposite a template abasic site more efficiently than opposite a template T, suggesting a role for human Pol(iota) in DNA lesion bypass. The unique features of preferential G incorporation opposite template T and T stop suggest that DNA Pol(iota) may additionally play a specialized function in human biology.

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Crossref · 10.1128/mcb.20.19.7099-7108.2000

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  • Pol η inserts dGTP opposite template T even more efficiently than it inserts A opposite T, so its error rate for this mispair approaches 1.

    “The most striking violation of Watson-Crick base pairing rules is exhibited by Pol , which inserts dGTP opposite template T even more efficiently than it inserts A opposite T (12-14), i.e. its error rate for this mispair approaches 1 (Fig. 1).”

    From DNA Replication Fidelity (2004) · cites this paper as [13]

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Authors
Zhang, Y., Yuan, F., Wu, X., & Wang, Z.
Affiliations
  • University of Kentucky (US)
  • Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536
Venue
Molecular and Cellular Biology
Published
2000-10-15
Volume
20
Issue
19
Pages
7099-7108
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2120072997
Cited by
200
References
40
Citations by year
2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 11
FWCI
6.38
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Burroughs Wellcome Fund
  • University of Kentucky
  • Francis Crick Institute
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 › Biochemical and Molecular Research
Keywords
DNA polymerase iota, Poli, non-Watson-Crick base pairing, base selection, DNA damage bypass, DNA replication, mutagenesis
MeSH terms
DNA Polymerase iota, DNA-Directed DNA Polymerase, DNA Replication, Genetic Code, Guanosine Triphosphate, Humans, Kinetics, Substrate Specificity, Templates, Genetic, Thymine Nucleotides, Mutagenesis, Base Pairing

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