Cited by 372DNA Repair MechanismsDNA and Nucleic Acid ChemistryGenetic factors in colorectal cancer

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Low fidelity DNA synthesis by human DNA polymerase-η

Matsuda, Toshiro, Bebenek, Katarzyna, Masutani, Chikahide, Hanaoka, Fumio, Kunkel, Thomas A.·2000·Nature

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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.

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Self-citation

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.
ORCID: Masutani, Chikahide
Hanaoka, Fumio
Kunkel, Thomas A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2000-04
Volume: 404
Issue: 6781
Pages: 1011-1013
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35010014
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

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Low fidelity DNA synthesis by human DNA polymerase-η

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