PMID:15598893

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Citation

Kamiya, H, Ishiguro, C and Harashima, H (2004) Increased A:T-->C:G mutations in the mutT strain upon 8-hydroxy-dGTP treatment: direct evidence for MutT involvement in the prevention of mutations by oxidized dGTP. J. Biochem. 136:359-62

Abstract

The Escherichia coli MutT protein hydrolyzes 8-hydroxy-dGTP (8-OH-dGTP) in vitro, and mutT gene deficiencies cause increased spontaneous A:T-->C:G mutations. However, no direct evidence exists for enhanced mutagenicity of 8-OH-dGTP in mutT cells. In this study, 8-OH-dGTP was introduced into wild type and mutT E. coli cells, and mutations of a chromosomal gene were monitored. 8-OH-dGTP induced mutations of the rpoB gene, the degree of the mutation induction in the mutT strain being approximately 6-fold higher than that in the wild type strain. On the other hand, 2-hydroxy-dATP, which is not a substrate of the MutT protein, increased the mutation to similar degrees in the two strains. These results constitute the first evidence that the MutT protein suppresses mutation by 8-OH-dGTP in vivo.

Links

PubMed Online version:10.1093/jb/mvh132

Keywords

Adenosine Triphosphate/chemistry; DNA Mutational Analysis; DNA-Directed RNA Polymerases/metabolism; Deoxyribonucleotides/chemistry; Deoxyribonucleotides/genetics; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/genetics; Guanosine Triphosphate/analogs & derivatives; Guanosine Triphosphate/chemistry; Guanosine Triphosphate/metabolism; Guanosine Triphosphate/pharmacology; Mutation; Oxygen/metabolism; Phosphoric Monoester Hydrolases/genetics; Pyrophosphatases

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