Cited by 632DNA Repair MechanismsDNA and Nucleic Acid ChemistryGenetic factors in colorectal cancer

Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions

Johnson, Robert E., Washington, M. Todd, Haracska, Lajos, Prakash, Satya, Prakash, Louise·2000·Nature

Abstract

DNA lesions can often block DNA replication, so cells possess specialized low-fidelity, and often error-prone, DNA polymerases that can bypass such lesions and promote replication of damaged DNA. The Saccharomyces cerevisiae RAD30 and human hRAD30A encode Pol eta, which bypasses a cis-syn thymine-thymine dimer efficiently and accurately. Here we show that a related human gene, hRAD30B, encodes the DNA polymerase Pol iota, which misincorporates deoxynucleotides at a high rate. To bypass damage, Pol iota specifically incorporates deoxynucleotides opposite highly distorting or non-instructional DNA lesions. This action is combined with that of DNA polymerase Pol zeta, which is essential for damage-induced mutagenesis, to complete the lesion bypass. Pol zeta is very inefficient in inserting deoxynucleotides opposite DNA lesions, but readily extends from such deoxynucleotides once they have been inserted. Thus, in a new model for mutagenic bypass of DNA lesions in eukaryotes, the two DNA polymerases act sequentially: Pol iota incorporates deoxynucleotides opposite DNA lesions, and Pol zeta functions as a mispair extender.

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Crossref · 10.1038/35023030

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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 [14]

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Authors
Johnson, R. E., Washington, M. T., Haracska, L., Prakash, S., & Prakash, L.
Affiliations
The University of Texas Medical Branch at Galveston (US)
Venue
Nature
Published
2000-08
Volume
406
Issue
6799
Pages
1015-1019
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2470508052
Cited by
632
References
21
Citations by year
2026: 9 · 2025: 8 · 2024: 7 · 2023: 14 · 2022: 9 · 2021: 16 · 2020: 21 · 2019: 15 · 2018: 9 · 2017: 17 · 2016: 14 · 2015: 17 · 2014: 21 · 2013: 18 · 2012: 34
FWCI
17.34
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Environmental Health Sciences
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
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
DNA polymerase iota, DNA polymerase zeta, DNA damage bypass, thymine-thymine dimers, error-prone DNA replication, misincorporation, DNA damage, Saccharomyces cerevisiae, human cells
MeSH terms
DNA Polymerase iota, Cloning, Molecular, Deoxyribonucleotides, DNA, DNA Damage, DNA-Directed DNA Polymerase, DNA Repair, HeLa Cells, Humans, Kinetics, Saccharomyces cerevisiae, Substrate Specificity, Base Pairing

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