Suppression of spontaneous and hydrogen peroxide‐induced mutations by a MutT‐type nucleotide pool sanitization enzyme, the Escherichia coli Orf135 protein

Background:  We recently found that the Escherichia coli Orf135 protein, a MutT‐type enzyme, hydrolysed 2‐hydroxy‐dATP (2‐OH‐dATP), and less efficiently, 8‐hydroxy‐dGTP. Results:  In this study, we examined the effects of the absence of the orf135 gene. Frequencies of spontaneous and H2O2‐induced mu...

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Published in:Genes to cells : devoted to molecular & cellular mechanisms 2003-12, Vol.8 (12), p.941-950
Main Authors: Kamiya, Hiroyuki, Iida, Emiko, Murata‐Kamiya, Naoko, Yamamoto, Yoshihiro, Miki, Takeyoshi, Harashima, Hideyoshi
Format: Article
Language:English
Subjects:
Base Sequence
Deoxyribonucleotides - metabolism
DNA Mutational Analysis
Escherichia coli
Escherichia coli - drug effects
Escherichia coli - enzymology
Escherichia coli - genetics
Escherichia coli Proteins - classification
Escherichia coli Proteins - genetics
Escherichia coli Proteins - physiology
Gene Expression
Hydrogen Peroxide - toxicity
Molecular Sequence Data
Mutation
Orf135 protein
Oxidation-Reduction
Phenotype
Phosphoric Monoester Hydrolases - classification
Pyrophosphatases - classification
Pyrophosphatases - genetics
Pyrophosphatases - physiology
Recombinant Proteins - metabolism
Reverse Transcriptase Polymerase Chain Reaction
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Summary:Background:  We recently found that the Escherichia coli Orf135 protein, a MutT‐type enzyme, hydrolysed 2‐hydroxy‐dATP (2‐OH‐dATP), and less efficiently, 8‐hydroxy‐dGTP. Results:  In this study, we examined the effects of the absence of the orf135 gene. Frequencies of spontaneous and H2O2‐induced mutations were two‐ to three‐fold higher in the orf135‐ strain than in the wild‐type strain. These mutations include various mutations involving a G:C→T:A transversion, the same type of mutation elicited by 2‐OH‐dATP. Over‐expression of the Orf135 protein suppressed mutations even in the wild‐type strain, as well as in the orf135‐ strain. Conclusions:  The mutator phenotype of bacteria lacking the Orf135 protein suggests that this protein is involved in the suppression of mutations induced by oxidized deoxynucleotides in vivo and that various MutT‐type enzymes contribute to nucleotide pool sanitization.
ISSN:1356-9597
1365-2443
DOI:10.1046/j.1365-2443.2003.00688.x