Oxidative nucleotide damage: Consequences and prevention

Mutsuo Sekiguchi, Teruhisa Tsuzuki

Research output: Contribution to journalReview article

163 Citations (Scopus)

Abstract

8-Oxoguanine (8-oxo-7,8-dihydroguanine) is produced in DNA, as well as in nucleotide pools of cells, by reactive oxygen species normally formed during cellular metabolic processes. 8-Oxoguanine nucleotide can pair with cytosine and adenine nucleotides with an almost equal efficiency, then transversion mutation ensues. MutT protein of Escherichia coli and related mammalian protein MTH1 specifically degrade 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing misincorporation of 8-oxoguanine into DNA. The bacterial and mammalian enzymes are close in their size and share a highly conserved region consisting of 23 residues with 14 identical amino acids. Following saturation mutagenesi of this region, most of these residues proved to be essential to exert 8-oxo-dGTPase activity. Gene targeting was done to establish MTH1-deficient cell lines and mice for study. When examined 18 months after birth, a greater number of tumors were formed in the lungs livers, and stomachs of MTH1-/- mice, as compared with findings in wild-type mice. These proteins protect genetic information from untoward effects of threats of endogenous oxygen.

Original languageEnglish
Pages (from-to)8895-8904
Number of pages10
JournalOncogene
Volume21
Issue number58 REV. ISS. 8
DOIs
Publication statusPublished - Dec 15 2002

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Sekiguchi, M., & Tsuzuki, T. (2002). Oxidative nucleotide damage: Consequences and prevention. Oncogene, 21(58 REV. ISS. 8), 8895-8904. https://doi.org/10.1038/sj.onc.1206023