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Mmh / Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice
Open accessAbstract
The major mutagenic base lesion in DNA caused by exposure to reactive oxygen species is 8-hydroxyguanine or 7,8-dihydro-8-oxoguanine (8-OH-G). Products of the human MMH / OGG1 gene are known to catalyze in vitro the reactions repairing this DNA lesion. To analyze the function of Mmh in vivo , we generated a mouse line carrying a mutant Mmh allele by targeted gene disruption. Mmh homozygous mutant mice were found to have a physically normal appearance, but to have lost nicking activity in liver extracts for substrate DNA containing 8-OH-G, exhibiting a 3-fold increased accumulation of this adduct at 9 weeks of age compared with wild-type or heterozygous mice. Further elevation to 7-fold was observed in 14-week-old animals. Substantial increase of spontaneous mutation frequencies was clearly identified in Mmh mutant mice bearing transgenic gpt genes. These results indicate that exposure of DNA to endogenous oxidative species continuously produces the mutagenic adduct 8-OH-G in mice, and Mmh plays an essential role in repair of this DNA damage.
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Citations
Cited by
Oxidative DNA damage and disease: induction, repair and significance
Evans, M. D., Dizdaroglu, M., & Cooke, M. S. (2004) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2003.11.001 · Cited by 1,372
Repair and Genetic Consequences of Endogenous DNA Base Damage in Mammalian Cells
Barnes, D. E., & Lindahl, T. (2004) · Annual Review of Genetics · doi:10.1146/annurev.genet.38.072902.092448 · Cited by 753
Repair of Endogenous DNA Damage
LINDAHL, T., & BARNES, D. E. (2000) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2000.65.127 · Cited by 714
Base excision repair and cancer
Wallace, S. S., Murphy, D. L., & Sweasy, J. B. (2012) · Cancer Letters · doi:10.1016/j.canlet.2011.12.038 · Cited by 329
Xie, Y., Yang, H., Cunanan, C., Okamoto, K., Shibata, D., Pan, J., Barnes, D. E., Lindahl, T., McIlhatton, M., Fishel, R., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3834 · Cited by 291
Metadata
- Authors
- Minowa, O., Arai, T., Hirano, M., Monden, Y., Nakai, S., Fukuda, M., Itoh, M., Takano, H., Hippou, Y., Aburatani, H., Masumura, K.-I., Nohmi, T., Nishimura, S., & Noda, T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-03-21
- Volume
- 97
- Issue
- 8
- Pages
- 4156-4161
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2154828075
- Cited by
- 348
- References
- 0
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Mmh / Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice. https://app.cochat.ai/papers/10.1073/pnas.050404497
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- Minowa, O., Arai, T., Hirano, M., Monden, Y., Nakai, S., Fukuda, M., Itoh, M., Takano, H., Hippou, Y., Aburatani, H., Masumura, K.-I., Nohmi, T., Nishimura, S., & Noda, T. (2000). Mmh / Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.050404497
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