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Preferential Incorporation of G Opposite Template T by the Low-Fidelity Human DNA Polymerase ι
Open accessAbstract
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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“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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Metadata
- 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
- Publisher
- Informa UK Limited
- Published
- 2000-10-15
- Volume
- 20
- Issue
- 19
- Pages
- 7099-7108
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC86254
- 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
- green
- europepmc.org
- 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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