Repair and mutagenesis at oxidized DNA lesions in the developing brain of wild-type and Ogg1−/− mice
| Autor: | Gaute Nesse, Erling Seeberg, Christine Gran, Elisabeth Larsen, Karen Reite, Arne Klungland |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research Guanine DNA Repair DNA damage DNA repair Biology medicine.disease_cause DNA Glycosylases Mice Western blot Genetics medicine Animals Mutation frequency Molecular Biology Mice Knockout medicine.diagnostic_test Homozygote Mutagenesis Wild type Brain Molecular biology Oxygen Oxidative Stress Gamma Rays DNA glycosylase Female Carcinogenesis DNA Damage |
| Zdroj: | Oncogene. 25:2425-2432 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1209284 |
| Popis: | OGG1 (8-oxoguanine DNA glycosylase-1) is one of the main DNA glycosylases present in mammalian cells. The enzyme removes 7,8-dihydro-8-oxoguanine (8-oxoG) lesions, believed to be the most important oxidized lesions due to their relatively high incidence and their miscoding properties. This study shows that in prenatal mice brains the repair capacity for 8-oxoG is 5-10-fold higher than in adult mice brains. Western blot analysis and repair activity in extracts from Ogg1(-/-) mice revealed that OGG1 was responsible for the efficient 8-oxoG removal from prenatal mice. To investigate how OGG1 protects against oxidative stress-induced mutagenesis, pregnant Big Blue/wild-type and Big Blue/Ogg1(-/-) mice were exposed to nontoxic doses of gamma radiation. A 2.5-fold increase in the mutation frequency in Ogg1(-/-) mouse brains was obtained by exposure to 3.5 Gy at day 19 postfertilization. This was largely due to GC to TA transversions, believed to originate from 8-oxoG mispairing with A during replication. Furthermore, rapid cell divisions seemed to be required for fixation of mutations, as a similar dose of radiation did not increase the mutation frequency, or the frequency of GC to TA transversion, in the adult brain. |
| Databáze: | OpenAIRE |
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