Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo- dGTP, a mutagenic substrate for DNA synthesis

K. Sakumi, M. Furuichi, T. Tsuzuki, T. Kakuma, S. I. Kawabata, H. Maki, M. Sekiguchi

Research output: Contribution to journalArticlepeer-review

366 Citations (Scopus)

Abstract

8-Oxoguanine (8-oxo-7, 8-dihydroguanine) is produced in DNA, as well as in nucleotide pools of cells, by active oxygen species normally formed during cellular metabolic processes. 8-Oxoguanine nucleotide can pair with cytosine and adenine nucleotides at almost equal efficiencies, and transversion mutation ensues. Human cells contain enzyme activity, which hydrolyzes 8- oxo-dGTP to 8-oxo-dGMP, and this enzyme is responsible for preventing misincorporation of 8-oxoguanine into DNA. We purified this particular human enzyme to physical homogeneity and determined a partial amino acid sequence. We then cloned the cDNA for human 8-oxo-dGTPase and examined its nucleotide sequence. The human protein comprises 156 amino acid residues and has some sequence homology with the Escherichia coli MutT protein, which has a distinct 8-oxo-dGTPase activity. When the human cDNA was expressed in E. coli mutT- mutant cells, there was a significant amount of 8-oxo-dGTPase activity. In such cells, the frequency of spontaneous mutation was greatly reduced. We propose that the human 8-oxo-dGTPase protects genetic information from the untoward effects of endogenous oxygen radicals.

Original languageEnglish
Pages (from-to)23524-23530
Number of pages7
JournalJournal of Biological Chemistry
Volume268
Issue number31
Publication statusPublished - 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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