2003 Fiscal Year Final Research Report Summary
Repair of oxidative DNA damage in Mammalian cells
| 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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| Keywords | DNA damage / DNA repair / base excision repair / oxidative DNA damage / glycosylase |
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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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[Journal Article] A Novel nuclear and mitochondrial glycosylases revealed by disruption of the mouse Nth1 gene encoding an endonuclease III : homologue for repair of thymine glycol.2002
Author(s)
Takao M, Kanno S, Shiromoto T, Hasegawa R, Ide H, Iikeda S, Sarker AH, Seki S, Xing JZ, Le XC, Weinfeld M, Kobayashi K, Miyazaki J, Muijtjens M, Hoeijmakers JHJ, van der Horst G, Yasui.
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Journal Title
EMBO J. 21
Pages: 3486-3493
Description
「研究成果報告書概要(欧文)」より
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