8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog

Katsuyoshi Fujikawa, Hiroyuki Yakushiji, Yusaku Nakabeppu, Toshinori Suzuki, Mitsuharu Masuda, Hiroshi Ohshima, Hiroshi Kasai

Research output: Contribution to journalArticle

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Abstract

The human mutT homolog, hMTH1, suppresses spontaneous mutations by degrading the endogeneous mutagen, 8-hydroxy-dGTP. We previously reported the broad substrate specificity of hMTH1, which also degrades the oxidatively damaged purine nucleotides, 2-hydroxy-dATP, 8-hydroxy-dATP, 2-hydroxy-ATP, and 8-hydroxy-GTP, in addition to 8-hydroxy-dGTP. In this paper, we describe the hMTH1 activity for 8-chloro-dGTP, which could be formed in inflamed tissue by the reaction of dGTP with hypochlorous acid, a product of myeloperoxidase from activated human neutrophils. The hMTH1 protein was mixed with 1-20 μM of 8-chloro-dGTP and 8-hydroxy-dGTP, and the reaction products were quantified by anion-exchange HPLC to measure the pyrophosphatase reaction rate. The kinetic parameters revealed that 8-chloro-dGTP was degraded by hMTH1 with 50% efficiency as compared with that of 8-hydroxy-dGTP. This result suggests that 8-chloro-dGTP is an intrinsic substrate for hMTH1.

Original languageEnglish
Pages (from-to)149-151
Number of pages3
JournalFEBS Letters
Volume512
Issue number1-3
DOIs
Publication statusPublished - Feb 13 2002

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Hypochlorous Acid
Nucleotides
Pyrophosphatases
Purine Nucleotides
Adenosinetriphosphate
Mutagens
Substrates
Substrate Specificity
Reaction products
Kinetic parameters
Peroxidase
Reaction rates
Anions
Ion exchange
Neutrophils
High Pressure Liquid Chromatography
Tissue
Mutation
8-chloro-2'-deoxyguanosine triphosphate
8-hydroxy-dGTP

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog. / Fujikawa, Katsuyoshi; Yakushiji, Hiroyuki; Nakabeppu, Yusaku; Suzuki, Toshinori; Masuda, Mitsuharu; Ohshima, Hiroshi; Kasai, Hiroshi.

In: FEBS Letters, Vol. 512, No. 1-3, 13.02.2002, p. 149-151.

Research output: Contribution to journalArticle

Fujikawa, Katsuyoshi ; Yakushiji, Hiroyuki ; Nakabeppu, Yusaku ; Suzuki, Toshinori ; Masuda, Mitsuharu ; Ohshima, Hiroshi ; Kasai, Hiroshi. / 8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog. In: FEBS Letters. 2002 ; Vol. 512, No. 1-3. pp. 149-151.
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