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

Low fidelity DNA synthesis by human DNA polymerase-η

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

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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Crossref · 10.1038/35010014

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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
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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