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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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“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]
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Metadata
- 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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