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 journalArticle

107 Citations (Scopus)

Abstract

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
JournalBiochemistry
Volume38
Issue number12
DOIs
Publication statusPublished - Mar 23 1999

Fingerprint

Ribonucleotides
Guanine
Cells
Nucleotides
Diphosphates
Guanylate Kinases
Deoxyribonucleotides
Ribonucleosides
Ribonucleotide Reductases
Phosphorylation
RNA Polymerase II
Substrates
Transcription
Guanosine Triphosphate
Metabolism
Reactive Oxygen Species
Phosphotransferases
RNA
Degradation
Oxidation

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Hayakawa, H., Hofer, A., Thelander, L., Kitajima, S., Cai, Y., Oshiro, S., ... Sekiguchi, M. (1999). Metabolic fate of oxidized guanine ribonucleotides in mammalian cells. Biochemistry, 38(12), 3610-3614. https://doi.org/10.1021/bi982361l

Metabolic fate of oxidized guanine ribonucleotides in mammalian cells. / Hayakawa, Hiroshi; Hofer, Anders; Thelander, Lars; Kitajima, Shigetaka; Cai, Yong; Oshiro, Satoru; Yakushiji, Hiroyuki; Nakabeppu, Yusaku; Kuwano, Michihiko; Sekiguchi, Mutsuo.

In: Biochemistry, Vol. 38, No. 12, 23.03.1999, p. 3610-3614.

Research output: Contribution to journalArticle

Hayakawa, H, Hofer, A, Thelander, L, Kitajima, S, Cai, Y, Oshiro, S, Yakushiji, H, Nakabeppu, Y, Kuwano, M & Sekiguchi, M 1999, 'Metabolic fate of oxidized guanine ribonucleotides in mammalian cells', Biochemistry, vol. 38, no. 12, pp. 3610-3614. https://doi.org/10.1021/bi982361l
Hayakawa H, Hofer A, Thelander L, Kitajima S, Cai Y, Oshiro S et al. Metabolic fate of oxidized guanine ribonucleotides in mammalian cells. Biochemistry. 1999 Mar 23;38(12):3610-3614. https://doi.org/10.1021/bi982361l
Hayakawa, Hiroshi ; Hofer, Anders ; Thelander, Lars ; Kitajima, Shigetaka ; Cai, Yong ; Oshiro, Satoru ; Yakushiji, Hiroyuki ; Nakabeppu, Yusaku ; Kuwano, Michihiko ; Sekiguchi, Mutsuo. / Metabolic fate of oxidized guanine ribonucleotides in mammalian cells. In: Biochemistry. 1999 ; Vol. 38, No. 12. pp. 3610-3614.
@article{1512643f564747388290b263a9e25f46,
title = "Metabolic fate of oxidized guanine ribonucleotides in mammalian cells",
abstract = "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.",
author = "Hiroshi Hayakawa and Anders Hofer and Lars Thelander and Shigetaka Kitajima and Yong Cai and Satoru Oshiro and Hiroyuki Yakushiji and Yusaku Nakabeppu and Michihiko Kuwano and Mutsuo Sekiguchi",
year = "1999",
month = "3",
day = "23",
doi = "10.1021/bi982361l",
language = "English",
volume = "38",
pages = "3610--3614",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "12",

}

TY - JOUR

T1 - Metabolic fate of oxidized guanine ribonucleotides in mammalian cells

AU - Hayakawa, Hiroshi

AU - Hofer, Anders

AU - Thelander, Lars

AU - Kitajima, Shigetaka

AU - Cai, Yong

AU - Oshiro, Satoru

AU - Yakushiji, Hiroyuki

AU - Nakabeppu, Yusaku

AU - Kuwano, Michihiko

AU - Sekiguchi, Mutsuo

PY - 1999/3/23

Y1 - 1999/3/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033596906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033596906&partnerID=8YFLogxK

U2 - 10.1021/bi982361l

DO - 10.1021/bi982361l

M3 - Article

C2 - 10090747

AN - SCOPUS:0033596906

VL - 38

SP - 3610

EP - 3614

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 12

ER -