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| Content Provider | PubMed Central |
|---|---|
| Author | Minowa, Osamu Arai, Tsuyoshi Hirano, Masanori Monden, Yoshiaki Nakai, Shigeyasu Fukuda, Mayuko Itoh, Masaki Takano, Hiroshi Yoshitaka, Hippou Hiroyuki, Aburatani Masumura, Ken-ichi Nohmi, Takehiko Nishimura, Susumu Noda, Tetsuo |
| Copyright Year | 2000 |
| Abstract | 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. |
| Starting Page | 4156 |
| File Format | |
| ISSN | 10916490 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 97 |
| Language | English |
| Publisher | The National Academy of Sciences |
| Publisher Date | 2000-04-11 |
| Access Restriction | Open |
| Rights Holder | The National Academy of Sciences |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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