Oxidative nucleotide damage: Consequences and prevention

Mutsuo Sekiguchi, Teruhisa Tsuzuki

研究成果: Contribution to journalReview article査読

167 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)8895-8904
ページ数10
ジャーナルOncogene
21
58 REV. ISS. 8
DOI
出版ステータス出版済み - 12 15 2002

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 遺伝学
  • 癌研究

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