Metabolic fate of oxidized guanine ribonucleotides in mammalian cells

Biochemistry. 1999 Mar 23;38(12):3610-4. doi: 10.1021/bi982361l.


8-Oxo-7,8-dihydroguanine- (8-oxoguanine-) containing nucleotides are generated in the cellular nucleotide pool by the action of oxygen radicals produced during normal cellular metabolism. We examined the interconversion and metabolic fate of 8-oxoguanine-containing ribonucleotides in mammalian cells. (1) 8-OxoGTP can be generated not only by direct oxidation of GTP but also by phosphorylation of 8-oxoGDP by nucleotide diphosphate kinase, and the 8-oxoGTP thus formed can serve as a substrate for RNA polymerase II to induce transcription errors. (2) MTH1 protein carrying intrinsic 8-oxo-dGTPase activity has the potential to hydrolyze 8-oxoGTP to 8-oxoGMP, thus preventing misincorporation of 8-oxoguanine into RNA. 8-OxoGMP, the degradation product, cannot be reutilized, since guanylate kinase, which has the potential to phosphorylate both GMP and dGMP, is inactive on 8-oxoGMP. (3) Ribonucleotide reductase, which catalyzes reduction of four naturally occurring ribonucleoside diphosphates, cannot convert 8-oxoguanine-containing ribonucleotide to the deoxyribonucleotide. This step appears to serve as a gatekeeper to prevent formation of mutagenic substrates for DNA synthesis from oxidized ribonucleotides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cells, Cultured
  • Guanine / analogs & derivatives*
  • Guanine / metabolism
  • Guanine / pharmacology
  • Guanine Nucleotides / metabolism
  • Guanosine Triphosphate / analogs & derivatives*
  • Guanosine Triphosphate / metabolism
  • Guanosine Triphosphate / pharmacology
  • Humans
  • Jurkat Cells
  • Mammals
  • RNA / biosynthesis
  • RNA / drug effects
  • RNA / metabolism
  • Ribonucleotide Reductases / metabolism*
  • Substrate Specificity
  • Swine


  • Guanine Nucleotides
  • 8-hydroxyguanosine triphosphate
  • 8-hydroxyguanine
  • Guanine
  • RNA
  • Guanosine Triphosphate
  • Ribonucleotide Reductases