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Novel nuclear and mitochondrial glycosylases revealed by disruption of the mouse Nth1 gene encoding an endonuclease III homolog for repair of thymine glycols
Author(s) -
Takao Masashi,
Kanno Shinichiro,
Shiromoto Tatsuya,
Hasegawa Rei,
Ide Hiroshi,
Ikeda Shogo,
Sarker Altraf H.,
Seki Shuji,
Xing James Z.,
Le X.Chris,
Weinfeld Michael,
Kobayashi Kumiko,
Miyazaki Junichi,
Muijtjens Manja,
Hoeijmakers Jan H.J.,
van der Horst Gijsbertus,
Yasui Akira
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf350
Subject(s) - biology , library science , national laboratory , physics , engineering physics , computer science
Endonuclease III, encoded by nth in Escherichia coli , removes thymine glycols (Tg), a toxic oxidative DNA lesion. To determine the biological significance of this repair in mammals, we established a mouse model with mutated mNth1 , a homolog of nth , by gene targeting. The homozygous mNth1 mutant mice showed no detectable phenotypical abnormality. Embryonic cells with or without wild‐type mNth1 showed no difference in sensitivity to menadione or hydrogen peroxide. Tg produced in the mutant mouse liver DNA by X‐ray irradiation disappeared with time, though more slowly than in the wild‐type mouse. In extracts from mutant mouse liver, we found, instead of mNTH1 activity, at least two novel DNA glycosylase activities against Tg. One activity is significantly higher in the mutant than in wild‐type mouse in mitochondria, while the other is another nuclear glycosylase for Tg. These results underscore the importance of base excision repair of Tg both in the nuclei and mitochondria in mammals.