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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.

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.

Pubmed ID: 12093749


  • Takao M
  • Kanno S
  • Shiromoto T
  • Hasegawa R
  • Ide H
  • Ikeda S
  • Sarker AH
  • Seki S
  • Xing JZ
  • Le XC
  • Weinfeld M
  • Kobayashi K
  • Miyazaki J
  • Muijtjens M
  • Hoeijmakers JH
  • van der Horst G
  • Yasui A
  • Sarker AH


The EMBO journal

Publication Data

July 1, 2002

Associated Grants

  • Agency: NIA NIH HHS, Id: AG17242-02

Mesh Terms

  • Alleles
  • Animals
  • Cell Nucleus
  • DNA
  • DNA Damage
  • DNA Repair
  • DNA, Mitochondrial
  • Deoxyribonuclease (Pyrimidine Dimer)
  • Endodeoxyribonucleases
  • Escherichia coli Proteins
  • Female
  • Gene Targeting
  • Liver
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondria, Liver
  • Mitochondrial Proteins
  • Oxidative Stress
  • Phenotype
  • Thymine