Roles of specialized DNA polymerases in mutagenesis by 8-hydroxyguanine in human cells
Open accessAbstract
The formation of 8-hydroxyguanine (8-OH-Gua, 7,8-dihydro-8-oxoguanine) in DNA and in the nucleotide pool results in G:C-->T:A and A:T-->C:G substitution mutations, respectively, due to the ability of 8-OH-Gua to pair with both C and A. In this study, shuttle plasmid DNAs containing 8-OH-Gua paired with C and A in the supF gene were transfected into human 293T cells, in which specialized DNA polymerases were knocked-down. The DNAs replicated in the cells were recovered and then introduced into an indicator strain of Escherichia coli. Mutation analysis indicated that the knock-downs of DNA polymerases eta and zeta by siRNAs enhanced the G:C-->T:A mutations caused by 8-OH-Gua:C. The 8-OH-Gua:C-induced mutation frequency was not further increased by double knock-downs of DNA polymerases eta and zeta, suggesting that the two DNA polymerases work in the same pathway. In addition, the reduction of DNA polymerase eta slightly decreased the A:T-->C:G substitutions caused by 8-OH-Gua:A. These results suggest that DNA polymerases eta and zeta are involved in the bypass of 8-OH-Gua in human cells.
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Pol eta can insert A or C opposite a site with 8-oxoG, which may result in a G to T transversion.
“Pol eta can insert A or C opposite a site with 8-oxoG, which may result in a G to T transversion.”
From Sunlight damage to cellular DNA: focus on oxidatively generated lesions (2017) · cites this paper as [109]
Pol eta can perform bypass, with moderate efficiency, of 8-oxoG, which has a potentially important role in the suppression of mutations due to this oxidatively generated DNA lesion in human cells.
“It can also perform the bypass, with moderate efficiency, of 8-oxoG, which has a potentially important role in the suppression of mutations due to this oxidatively generated DNA lesion in human cells [109,271].”
From Sunlight damage to cellular DNA: focus on oxidatively generated lesions (2017) · cites this paper as [109]
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Sunlight damage to cellular DNA: focus on oxidatively generated lesions
Schuch, A. P., Moreno, N. C., Schuch, N. J., Menck, C. F. M., & Garcia, C. C. M. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.01.029 · Cited by 436 · see citing works
- Authors
- Kamiya, H., Yamaguchi, A., Suzuki, T., & Harashima, H.
- Affiliations
- Hokkaido University (JP)
- Corresponding author
- Kamiya, Hiroyuki
- Venue
- Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 686
- Issue
- 1-2
- Pages
- 90-95
- ISSN
- 0027-5107 (ISSN-L)
- 1386-1964
- OpenAlex
- W2048816529
- Cited by
- 40
- References
- 54
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 2
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Mutation research. Fundamental and molecular mechanisms of mutagenesis (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- 8-oxoguanine, DNA polymerase eta, DNA polymerase zeta, mutagenesis, nucleotide pools, DNA replication, transfection, siRNA knockdown, HEK293T cells, mutational pathways
- MeSH terms
- Y-Family DNA Polymerases, DNA-Directed DNA Polymerase, Guanine, Humans, Plasmids, Mutagenesis
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