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  • The EMBO Journal (2002) 21, 3486 - 3493
  • doi:10.1093/emboj/cdf350



There is a Corrigendum (August 2002) associated with this Article.

Novel nuclear and mitochondrial glycosylases revealed by disruption of the mouse Nth1 gene encoding an endonuclease III homolog for repair of thymine glycols

Masashi Takao1,11, Shin-ichiro Kanno1,11, Tatsuya Shiromoto2, Rei Hasegawa2, Hiroshi Ide2, Shogo Ikeda3, Altraf H. Sarker4,5, Shuji Seki4,6, James Z. Xing7, X.Chris Le7, Michael Weinfeld8, Kumiko Kobayashi1, Jun-ichi Miyazaki9, Manja Muijtjens10, Jan H.J. Hoeijmakers10, Gijsbertus van der Horst10 and Akira Yasui1

  1. Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan
  2. Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526, Japan
  3. Department of Biochemistry, Faculty of Science, Okayama University of Science, Okayama 700-0005, Japan
  4. Department of Molecular Biology, Institute of Cellular and Molecular Biology, Okayama University Medical School, Okayama 700-8558, Japan
  5. Present address: Department of Cell and Molecular Biology, Life Sciences Division, M.S. 74–157 Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
  6. Present address: Department of Human Nutrition, Chugoku Junior College, Okayama, Japan
  7. Department of Public Health Sciences, Faculty of Medicine, University of Alberta, Edmonton, Alberta T6G 2G3, Canada
  8. Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada
  9. Division of Stem Cell Regulation Research, Osaka University Medical School, Suita 565-0871, Japan
  10. MGC, Department of Cell Biology and Genetics, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands
  11. M.Takao and S.-i.Kanno contributed equally to this work

Correspondence to:

Akira Yasui, E-mail: ayasui@idac.tohoku.ac.jp

Received 7 January 2002; Accepted 14 May 2002; Revised 25 March 2002

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.

  • Keywords:

    • base excision repair,
    • DNA glycosylase,
    • endonuclease III,
    • mitochondria,
    • thymine glycol