The DOI matches its Crossref record; 67 of the 68 references it cites were found in a registry or an index.
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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Cites
The Genome Sequence of Drosophila melanogaster
Adams, M. D., Celniker, S., Holt, R. A., Evans, C. A., Gocayne, J. D., Amanatides, P. G., Scherer, S. E., Li, P. W., Hoskins, R. A., Galle, R. F., et al. (2000) · Science · doi:10.1126/science.287.5461.2185 · Cited by 5,902
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η
Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., & Hanaoka, F. (1999) · Nature · doi:10.1038/21447 · Cited by 1,292
Efficient Bypass of a Thymine-Thymine Dimer by Yeast DNA Polymerase, Polη
Johnson, R. E., Prakash, S., & Prakash, L. (1999) · Science · doi:10.1126/science.283.5404.1001 · Cited by 736
hRAD30 Mutations in the Variant Form of Xeroderma Pigmentosum
Johnson, R. E., Kondratick, C. M., Prakash, S., & Prakash, L. (1999) · Science · doi:10.1126/science.285.5425.263 · Cited by 732
Thymine-Thymine Dimer Bypass by Yeast DNA Polymerase ζ
Nelson, J. R., Lawrence, C. W., & Hinkle, D. C. (1996) · Science · doi:10.1126/science.272.5268.1646 · Cited by 660
Kato, T., & Shinoura, Y. (1977) · Molecular and General Genetics MGG · doi:10.1007/bf00283484 · Cited by 569
UmuD′ 2 C is an error-prone DNA polymerase, Escherichia coli pol V
Tang, M., Shen, X., Frank, E. G., O’Donnell, M. E., Woodgate, R., & Goodman, M. F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.16.8919 · Cited by 537
Self-citationThe dinB Gene Encodes a Novel E. coli DNA Polymerase, DNA Pol IV, Involved in Mutagenesis
Wagner, J. E., Grúz, P., Kim, S.-R., Yamada, M., Matsui, K., Fuchs, R. P., & Nohmi, T. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80376-7 · Cited by 474
Roles of E. coli DNA polymerases IV and V in lesion-targeted and untargeted SOS mutagenesis
Tang, M., Pham, P., Shen, X., Taylor, J.-S., O'Donnell, M., Woodgate, R., & Goodman, M. F. (2000) · Nature · doi:10.1038/35010020 · Cited by 443
Self-citationMasutani, C., Araki, M., Yamada, A., Kusumoto, R., Nogimori, T., Maekawa, T., Iwai, S., & Hanaoka, F. (1999) · The EMBO Journal · doi:10.1093/emboj/18.12.3491 · Cited by 434
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Wang, Z. (2005) · CRC Press eBooks · doi:10.1201/9780849352683.ch24
Palacka, P., Holíčková, A., Roška, J., Makovický, P., Vallová, M., Biró, C., Órásová, E., Obertová, J., Mardiak, J., Ward, T. A., et al. (2024) · BMC Cancer · doi:10.1186/s12885-024-12865-8
“POLI is highly error-prone when replicating undamaged DNA, exhibiting an unusual misincorporation spectrum [31].”
BackgroundDCLRE1A orchestrates CAG repeat contraction following Cas12a-induced DNA breaksPreprint
Dabrowska, M., Siegner, S. M., Misiukiewicz, A., Bandaruk, Y., Schröder, M., Muhar, M., Kreutzer, S., Corn, J. E., & Olejniczak, M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.18.689026
Caractérisation fonctionnelle de la tolérance aux endommagements de l’ADN des embryons précoces
Furno, E. L. (2019) · theses.fr (ABES) · doi:10.70675/cf32bcd5z3031z4693z8b1bz62fe76673ccc
Engel, B., Szikriszt, B., Gyüre, Z., Sale, J. E., Szüts, D., & Németh, E. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2526551123
Interplay Between Base Editing and DNA repair: From Molecular Mechanisms to Clinical Translation
Tao, R., Li, M., Luo, T., & Yao, S. (2026) · Biotechnology Advances · doi:10.1016/j.biotechadv.2026.109018
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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