polι, a remarkably error-prone human DNA polymerase
Open accessAbstract
The Saccharomyces cerevisiae RAD30 gene encodes DNA polymerase η. Humans possess two Rad30 homologs. One ( RAD30A/POLH ) has previously been characterized and shown to be defective in humans with the Xeroderma pigmentosum variant phenotype. Here, we report experiments demonstrating that the second human homolog ( RAD30B ), also encodes a novel DNA polymerase that we designate polι. polι, is a distributive enzyme that is highly error-prone when replicating undamaged DNA. At template G or C, the average error frequency was ∼1 × 10 −2 . Our studies revealed, however, a striking asymmetry in misincorporation frequency at template A and T. For example, template A was replicated with the greatest accuracy, with misincorporation of G, A, or C occurring with a frequency of ∼1 × 10 −4 to 2 × 10 −4 . In dramatic contrast, most errors occurred at template T, where the misincorporation of G was, in fact, favored ∼3:1 over the correct nucleotide, A, and misincorporation of T occurred at a frequency of ∼6.7 × 10 −1 . These findings demonstrate that polι is one of the most error-prone eukaryotic polymerases reported to date and exhibits an unusual misincorporation spectrum in vitro.
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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 [12]
The Results section reports that G insertion opposite template T is favored about 3:1 over A insertion, but this measurement is for polymerase ι, not polymerase η. The “Preliminary characterization of human pol” section explicitly identifies the enzyme studied as human DNA polymerase iota, so the claim assigns its finding to the wrong enzyme. No page numbers are available in our copy. (LLM, conf=0.88)
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Yeast Rev1 Protein Is a G Template-specific DNA Polymerase
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Self-citation
- Authors
- Tissier, A., McDonald, J. P., Frank, E. G., & Woodgate, R.
- Affiliations
- National Institutes of Health (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-07-01
- Volume
- 14
- Issue
- 13
- Pages
- 1642-1650
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316739
- OpenAlex
- W1908705633
- Cited by
- 315
- References
- 68
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 7 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 11 · 2016: 9 · 2015: 10 · 2014: 9 · 2013: 11 · 2012: 11
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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 eta, error-prone DNA replication, xeroderma pigmentosum variant, Saccharomyces cerevisiae
- MeSH terms
- Base Sequence, DNA-Directed DNA Polymerase, Humans, Isoenzymes, Mutation, DNA Primers
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