| Project/Area Number |
13480162
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
YASUI Akira Tohoku Univ., 1DAC, Dept.Mol.genetics, Prof, 加齢医学研究所, 教授 (60191110)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAO Masashi Tohoku Univ., 1DAC, Dept.Mol.genetics, Lecturer, 加齢医学研究所, 講師 (70216612)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2002: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2001: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | DNA damage / DNA repair / base excision repair / oxidative DNA damage / glycosylase / 活性酸素 / 発がん / 老化 / 単鎖切断 / ポリADPリボシル化 / XRCC1 / UVDE / チミングリコール / ノックアウトマウス / ミトコンドリア |
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| Research Abstract |
Endonuclease III, encoded by nth in Escherichia coli, removes thymine glycols, a toxic oxidative DNA lesion. To determine the biological significance of this repair in mammals, we established a mouse mutated in mNth1, a homologue of nth, by gene targeting. The homozygous mNth1 mutant mouse showed no detectable phenotypic abnormality so far analyzed. Embryonic cells with or without wild-type mNth1 showed no difference in sensitivity to menadione or hydrogen peroxide. Thymine glycols produced in the mutant mouse liver DNA by X-ray irradiation disappeared with time, though more slowly than in wild-type mouse. In extracts from mutant mouse liver, we found, instead of mNTH1 activity, at least two novel DNA glycosylase activities against thymine glycols. One activity is significantly higher in the mutant than in wild-type mouse in mitochondria, while the other is another nuclear glycosylase, for thymine glycols. These results underscore the importance of base excision repair of thymine glycols both in the nuclei and in the mitochondria in mammals.
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