The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Preferential cis–syn thymine dimer bypass by DNA polymerase η occurs with biased fidelity
Abstract
Human DNA polymerase eta (Pol eta) modulates susceptibility to skin cancer by promoting DNA synthesis past sunlight-induced cyclobutane pyrimidine dimers that escape nucleotide excision repair (NER). Here we have determined the efficiency and fidelity of dimer bypass. We show that Pol eta copies thymine dimers and the flanking bases with higher processivity than it copies undamaged DNA, and then switches to less processive synthesis. This ability of Pol eta to sense the dimer location as synthesis proceeds may facilitate polymerase switching before and after lesion bypass. Pol eta bypasses a dimer with low fidelity and with higher error rates at the 3' thymine than at the 5' thymine. A similar bias is seen with Sulfolobus solfataricus DNA polymerase 4, which forms a Watson-Crick base pair at the 3' thymine of a dimer but a Hoogsteen base pair at the 5' thymine (ref. 3). Ultraviolet-induced mutagenesis is also higher at the 3' base of dipyrimidine sequences. Thus, in normal people and particularly in individuals with NER-defective xeroderma pigmentosum who accumulate dimers, errors made by Pol eta during dimer bypass could contribute to mutagenesis and skin cancer.
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“This may have implications for the fidelity of lesion bypass, because both Dpo4 and human Pol have higher fidelity at the 5Ј T of a dimer than at the 3Ј T, and surprisingly, the fidelity of human Pol is slightly higher at the 5Ј T of a dimer than at the equivalent undamaged T (47).”
From DNA Replication Fidelity (2004) · cites this paper as [47]
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Cites
Friedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A., & Ellenberger, T. (2005) · doi:10.1128/9781555816704 · Cited by 5,683
Bootsma, D., & Hoeijmakers, J. H. J. (1996) · Trends in Genetics · doi:10.1016/0168-9525(96)81408-9 · Cited by 2,285
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-citationhRAD30 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
Crystal Structure of a Y-Family DNA Polymerase in Action
Ling, H., Boudsocq, F., Woodgate, R., & Yang, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00515-3 · Cited by 610
Mechanisms of accurate translesion synthesis by human DNA polymerase η
Masutani, C., Kusumoto, R., Iwai, S., & Hanaoka, F. (2000) · The EMBO Journal · doi:10.1093/emboj/19.12.3100 · Cited by 504
Self-citationFidelity of Human DNA Polymerase η
Johnson, R. E., Washington, M. T., Prakash, S., & Prakash, L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.11.7447 · Cited by 399
Low fidelity DNA synthesis by human DNA polymerase-η
Matsuda, T., Bebenek, K., Masutani, C., Hanaoka, F., & Kunkel, T. A. (2000) · Nature · doi:10.1038/35010014 · Cited by 372
Self-citationStructure of the Catalytic Core of S. cerevisiae DNA Polymerase η
Trincão, J., Johnson, R. E., Escalante, C. R., Prakash, S., Prakash, L., & Aggarwal, A. K. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00306-9 · Cited by 348
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Gaillard, H., García‐Muse, T., & Aguilera, A. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3916 · Cited by 1,134
Interaction of Human DNA Polymerase η with Monoubiquitinated PCNA
Kannouche, P. L., Wing, J., & Lehmann, A. R. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00259-x · Cited by 845
Kunkel, T. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r400006200 · Cited by 754
Self-citationEukaryotic 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
The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases
McCulloch, S. D., & Kunkel, T. A. (2008) · Cell Research · doi:10.1038/cr.2008.4 · Cited by 569
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Metadata
- Authors
- McCulloch, S. D., Kokoska, R. J., Masutani, C., Iwai, S., 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
- 2004-03
- Volume
- 428
- Issue
- 6978
- Pages
- 97-100
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1581236180
- Cited by
- 246
- References
- 30
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 9 · 2017: 9 · 2016: 9 · 2015: 15 · 2014: 9 · 2013: 12 · 2012: 12
- FWCI
- 8.17
- 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)
- Funders
- Wellcome Trust
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- DNA polymerase eta, cyclobutane pyrimidine dimers, polymerase fidelity, polymerase processivity, nucleotide excision repair, xeroderma pigmentosum, UV mutagenesis, Hoogsteen base pairing, skin cancer predisposition
- MeSH terms
- Y-Family DNA Polymerases, DNA, DNA Damage, DNA-Directed DNA Polymerase, Humans, Hydrogen Bonding, Pyrimidine Dimers, Mutagenesis, Sulfolobus, Base Pairing
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