NDX-1 protein hydrolyzes 8-oxo-7, 8-dihydrodeoxyguanosine-5′- diphosphate to sanitize oxidized nucleotides and prevent oxidative stress in Caenorhabditis elegans

U. Sanada, Shinichirou Yonekura, Masahiro Kikuchi, Kazunari Hashiguchi, Nobuya Nakamura, Shuji Yonei, Qiu Mei Zhang-Akiyama

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

8-oxo-dGTP is generated in the nucleotide pool by direct oxidation of dGTP or phosphorylation of 8-oxo-dGDP. It can be incorporated into DNA during replication, which would result in mutagenic consequences. The frequency of spontaneous mutations remains low in cells owing to the action of enzymes degrading such mutagenic substrates. Escherichia coli MutT and human MTH1 hydrolyze 8-oxo-dGTP to 8-oxo-dGMP. Human NUDT5 as well as human MTH1 hydrolyze 8-oxo-dGDP to 8-oxo-dGMP. These enzymes prevent mutations caused by misincorporation of 8-oxo-dGTP into DNA. In this study, we identified a novel MutT homolog (NDX-1) of Caenorhabditis elegans that hydrolyzes 8-oxo-dGDP to 8-oxo-dGMP. NDX-1 did not hydrolyze 8-oxo-dGTP, 2-hydroxy-dATP or 2-hydroxy-dADP. Expression of NDX-1 significantly reduced spontaneous A:T to C:G transversions and mitigated the sensitivity to a superoxide-generating agent, methyl viologen, in an E. coli mutT mutant. In C. elegans, RNAi of ndx-1 did not affect the lifespan of the worm. However, the sensitivity to methyl viologen and menadione bisulfite of the ndx-1-RNAi worms was enhanced compared with that of the control worms. These facts indicate that NDX-1 is involved in sanitization of 8-oxo-dGDP and plays a critical role in defense against oxidative stress in C. elegans.

Original languageEnglish
Pages (from-to)649-657
Number of pages9
JournalJournal of Biochemistry
Volume150
Issue number6
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

Fingerprint

Oxidative stress
Diphosphates
Caenorhabditis elegans
Oxidative Stress
Nucleotides
Paraquat
RNA Interference
Escherichia coli
Proteins
Vitamin K 3
Phosphorylation
DNA
Mutation Rate
Enzymes
DNA Replication
Superoxides
Oxidation
Mutation
8-oxo-7-hydrodeoxyguanosine
8-oxodeoxyguanosine triphosphate

Keywords

  • 8-oxo-dGDPase
  • Caenorhabditis elegans
  • mutations
  • NDX-1
  • oxidative stress
  • sanitization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

NDX-1 protein hydrolyzes 8-oxo-7, 8-dihydrodeoxyguanosine-5′- diphosphate to sanitize oxidized nucleotides and prevent oxidative stress in Caenorhabditis elegans. / Sanada, U.; Yonekura, Shinichirou; Kikuchi, Masahiro; Hashiguchi, Kazunari; Nakamura, Nobuya; Yonei, Shuji; Zhang-Akiyama, Qiu Mei.

In: Journal of Biochemistry, Vol. 150, No. 6, 12.2011, p. 649-657.

Research output: Contribution to journalArticle

Sanada, U. ; Yonekura, Shinichirou ; Kikuchi, Masahiro ; Hashiguchi, Kazunari ; Nakamura, Nobuya ; Yonei, Shuji ; Zhang-Akiyama, Qiu Mei. / NDX-1 protein hydrolyzes 8-oxo-7, 8-dihydrodeoxyguanosine-5′- diphosphate to sanitize oxidized nucleotides and prevent oxidative stress in Caenorhabditis elegans. In: Journal of Biochemistry. 2011 ; Vol. 150, No. 6. pp. 649-657.
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AU - Kikuchi, Masahiro

AU - Hashiguchi, Kazunari

AU - Nakamura, Nobuya

AU - Yonei, Shuji

AU - Zhang-Akiyama, Qiu Mei

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AB - 8-oxo-dGTP is generated in the nucleotide pool by direct oxidation of dGTP or phosphorylation of 8-oxo-dGDP. It can be incorporated into DNA during replication, which would result in mutagenic consequences. The frequency of spontaneous mutations remains low in cells owing to the action of enzymes degrading such mutagenic substrates. Escherichia coli MutT and human MTH1 hydrolyze 8-oxo-dGTP to 8-oxo-dGMP. Human NUDT5 as well as human MTH1 hydrolyze 8-oxo-dGDP to 8-oxo-dGMP. These enzymes prevent mutations caused by misincorporation of 8-oxo-dGTP into DNA. In this study, we identified a novel MutT homolog (NDX-1) of Caenorhabditis elegans that hydrolyzes 8-oxo-dGDP to 8-oxo-dGMP. NDX-1 did not hydrolyze 8-oxo-dGTP, 2-hydroxy-dATP or 2-hydroxy-dADP. Expression of NDX-1 significantly reduced spontaneous A:T to C:G transversions and mitigated the sensitivity to a superoxide-generating agent, methyl viologen, in an E. coli mutT mutant. In C. elegans, RNAi of ndx-1 did not affect the lifespan of the worm. However, the sensitivity to methyl viologen and menadione bisulfite of the ndx-1-RNAi worms was enhanced compared with that of the control worms. These facts indicate that NDX-1 is involved in sanitization of 8-oxo-dGDP and plays a critical role in defense against oxidative stress in C. elegans.

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