The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Low fidelity DNA synthesis by human DNA polymerase-η
Abstract
A superfamily of DNA polymerases that bypass lesions in DNA has been described. Some family members are described as error-prone because mutations that inactivate the polymerase reduce damage-induced mutagenesis. In contrast, mutations in the skin cancer susceptibility gene XPV, which encodes DNA polymerase (pol)-eta, lead to increased ultraviolet-induced mutagenesis. This, and the fact that pol-eta primarily inserts adenines during efficient bypass of thymine-thymine dimers in vitro, has led to the description of pol-eta as error-free. However, here we show that human pol-eta copies undamaged DNA with much lower fidelity than any other template-dependent DNA polymerase studied. Pol-eta lacks an intrinsic proofreading exonuclease activity and, depending on the mismatch, makes one base substitution error for every 18 to 380 nucleotides synthesized. This very low fidelity indicates a relaxed requirement for correct base pairing geometry and indicates that the function of pol-eta may be tightly controlled to prevent potentially mutagenic DNA synthesis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“DNA pol h copies undamaged DNA with a lower fidelity than most DNA-directed polymerases with an average base-substitution error rate of 3.5 £ 10 ¡2 [22][23][24] .”
From DNA polymerase η mutational signatures are found in a variety of different types of cancer (2018) · cites this paper as [22]
In the citing paper
“The mutable motif of pol h, the short motif WA/TW (W = A or T) was delineated in the context of somatic hypermutations and in vitro systems 22,23 .”
From DNA polymerase η mutational signatures are found in a variety of different types of cancer (2018) · cites this paper as [22]
Citations
Cites
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
Self-citationKunkel, T. A., & Bebenek, K. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.497 · Cited by 1,003
Self-citationThe accuracy of reverse transcriptase from HIV-1
Roberts, J. D., Bebenek, K., & Kunkel, T. A. (1988) · Science · doi:10.1126/science.2460925 · Cited by 997
Self-citationEfficient 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
Masutani, 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
Self-citationKim, S.-R., Maenhaut-Michel, G., Yamada, M., Yamamoto, Y., Matsui, K., Sofuni, T., Nohmi, T., & Ohmori, H. (1997) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.94.25.13792 · Cited by 343
MAHER, V. M., OUELLETTE, L. M., CURREN, R. D., & MCCORMICK, J. J. (1976) · Nature · doi:10.1038/261593a0 · Cited by 333
McDonald, J. P., Levine, A. S., & Woodgate, R. (1997) · Genetics · doi:10.1093/genetics/147.4.1557 · Cited by 314
A plethora of lesion-replicating DNA polymerasesPreprint
Woodgate, R. (1999) · Genes & Development · doi:10.1101/gad.13.17.2191 · Cited by 246
[18] Analyzing fidelity of DNA polymerases
Bębenek, K., & Kunkel, T. A. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)62020-6 · Cited by 198
Self-citationFidelity and Processivity of Saccharomyces cerevisiae DNA Polymerase η
Washington, M. T., Johnson, R. E., Prakash, S., & Prakash, L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.52.36835 · Cited by 181
The fidelity of DNA synthesis catalyzed by derivatives of Escherichia coli DNA polymerase I.
Bębenek, K., Joyce, C. M., Fitzgerald, M. P., & Kunkel, T. A. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)77430-9 · Cited by 175
Self-citationThe Fidelity of DNA Polymerase β during Distributive and Processive DNA Synthesis
Osheroff, W. P., Jung, H. K., Beard, W. A., Wilson, S. H., & Kunkel, T. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.6.3642 · Cited by 142
Self-citationOgi, T., Kato, T., Kato, T., & Ohmori, H. (1999) · Genes to Cells · doi:10.1046/j.1365-2443.1999.00289.x · Cited by 141
Bridging the gap: A family of novel DNA polymerases that replicate faulty DNA
Johnson, R. E., Washington, M. T., Prakash, S., & Prakash, L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12224 · Cited by 134
Perrino, F. W., & Loeb, L. A. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)81697-6 · Cited by 126
Novel DNA Polymerases Offer Clues to the Molecular Basis of Mutagenesis
Friedberg, E. C., & Gerlach, V. L. (1999) · Cell · doi:10.1016/s0092-8674(00)81970-4 · Cited by 121
Wang, H., Lawrence, C. W., Li, G., & Hays, J. B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.24.16894 · Cited by 103
Ultraviolet mutagenesis of normal and xeroderma pigmentosum variant human fibroblasts
Myhr, B., Turnbull, D., & DiPaolo, J. A. (1979) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(79)90089-7 · Cited by 76
Wang, Y., Maher, V. M., & McCormick, J. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.17.7810 · Cited by 71
Ultraviolet Hypermutablity of a Shuttle Vector Propagated in Xeroderma Pigmentosum Variant Cells
Waters, H. L., Seetharam, S., Seidman, M. M., & Kraemer, K. H. (1993) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12371686 · Cited by 65
Wang, Y.-C., Maher, V. M., Mitchell, D. L., & McCormick, J. J. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.7.4276-4283.1993 · Cited by 61
Kang, X. L., Yadao, F., Gietz, R. D., & Kunz, B. A. (1992) · Genetics · doi:10.1093/genetics/130.2.285 · Cited by 56
LEWIS, D. A., Bębenek, K., Beard, W. A., Wilson, S. H., & Kunkel, T. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.46.32924 · Cited by 48
Self-citationClairmont, C., Narayanan, L., Sun, K.-W., Glazer, P. M., & Sweasy, J. B. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.17.9580 · Cited by 41
Flagged first, then by citations
Research works printed but not linked: 1
- Roberts,J. D. & Kunkel,T. A. in DNA Replication in Eukaryotic Cells: Concepts, Enzymes and Systems (ed. Pamphilis, M. D.) 217 –247 (Cold Spring Harbor Laboratory Press, New York, 1996).
Cited by
Sorted by citations
Error-Prone Repair DNA Polymerases in Prokaryotes and Eukaryotes
Goodman, M. F. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.083101.124707 · Cited by 727
Hübscher, U., Maga, G., & Spadari, S. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.090501.150041 · Cited by 691
Molecular Mechanism of Class Switch Recombination: Linkage with Somatic Hypermutation
Honjo, T., Kinoshita, K., & Muramatsu, M. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.090501.112049 · Cited by 610
Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance
Waters, L. S., Minesinger, B. K., Wiltrout, M. E., D'Souza, S., Woodruff, R. V., & Walker, G. C. (2009) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00034-08 · Cited by 591
Regulation of monoubiquitinated PCNA by DUB autocleavage
Huang, T. T., Nijman, S. M. B., Mirchandani, K. D., Galardy, P. J., Cohn, M. A., Haas, W., Gygi, S. P., Ploegh, H. L., Bernards, R., & D’Andrea, A. D. (2006) · Nature Cell Biology · doi:10.1038/ncb1378 · Cited by 597
Metadata
- Authors
- Matsuda, T., Bebenek, K., Masutani, C., Hanaoka, F., & Kunkel, T. A.
- Affiliations
- National Institutes of Health (US)
- The University of Osaka (JP)
- RIKEN (JP)
- Corresponding author
- Kunkel, Thomas A.
- Venue
- Nature
- Published
- 2000-04
- Volume
- 404
- Issue
- 6781
- Pages
- 1011-1013
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1581466567
- Cited by
- 372
- References
- 27
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 8 · 2017: 12 · 2016: 15 · 2015: 16 · 2014: 10 · 2013: 16 · 2012: 9
- FWCI
- 15.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- 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, DNA synthesis fidelity, error-prone DNA replication, thymine-thymine dimers, DNA damage bypass, proofreading exonuclease, XPA, mutagenesis
- MeSH terms
- DNA Polymerase iota, Y-Family DNA Polymerases, DNA, DNA Damage, DNA-Directed DNA Polymerase, DNA Repair, Humans, Mutagenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
