Repair mechanism of oxidative DNA damage on the mitochondrial genome
| Project/Area Number |
13680618
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Tohoku University |
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Principal Investigator |
MASASHI Takao Institute of Development, Aging and Cancer., 加齢医学研究所, 助手 (70216612)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Reactive oxygen species / Mitochondrion / DNA repair / Aging / Cancer / Knock-out mouse / Base excision repair / DNAグリコシラーゼ |
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| Research Abstract |
This research is a basic investigation to evaluate the importance of DNA repair on the mitochondrial genome in view of cancer protection and aging process. For this purpose mutant mice that lack NTH1, a key enzyme removing oxidative pyrimidine base lesions from mitochondrial and nuclear DNA, was generated. The Nth1 knock-out did not lead to any abnormal mouse phenotype nor to sensitivity against oxidative stress. These results provoked us to find residual repair activities in the mutant mouse cells. With a biochemical approach, one residual DNA glycosylase activity in the mitochondrial extracts and, at least, two activities in the nuclear extracts were found. We analyzed three candidate genes in the database for the biochemically detected activities, and found that a gene named Neil1 encodes one of the nuclear DNA glycosylases. These results clearly indicate that mammalian base excision repair for oxidative pyrimidines can be initiated by multiple DNA glycosylases in both nucleus and mitochondrion, raising questions toward further studies, such as why and how the cells use different enzymes.
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Report
(3 results)
Research Products
(13 results)
