Metabolic fate of oxidized guanine ribonucleotides in mammalian cells

Hiroshi Hayakawa, Anders Hofer, Lars Thelander, Shigetaka Kitajima, Yong Cai, Satoru Oshiro, Hiroyuki Yakushiji, Yusaku Nakabeppu, Michihiko Kuwano, Mutsuo Sekiguchi

Research output: Contribution to journalArticlepeer-review

128 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3610-3614
Number of pages5
Issue number12
Publication statusPublished - Mar 23 1999

All Science Journal Classification (ASJC) codes

  • Biochemistry


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