Functional cooperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucleotide in Escherichia coli

Mutat Res. 1995 May;336(3):257-67. doi: 10.1016/0921-8777(94)00062-b.

Abstract

8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is a potent mutagenic substrate for DNA synthesis. The accumulation of 8-oxo-dGTP in the nucleotide pool induces G:C-->T:A transversion as well as A:T-->C:G transversion, and Escherichia coli cells possess mechanisms for preventing such mutations. The mutT gene product specifically hydrolyzes 8-oxo-dGTP to the monophosphate form while the mutM and the mutY gene products function to correct mispairs caused by incorporation of 8-oxoguanine into DNA. From analyses of forward mutations induced in cells lacking 8-oxo-dGTPase (MutT protein) and/or repair enzymes that suppress mutations caused by 8-oxoguanine in DNA (MutM and MutY proteins), cooperative functions of these proteins in control of the spontaneous mutagenesis became evident. In mutator strains lacking MutT and/or MutM proteins, 8-oxoguanine of DNA increased to a concentration expected from the increased rate of mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Bacterial Proteins / physiology*
  • Base Sequence
  • DNA Glycosylases*
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA, Bacterial / metabolism
  • DNA-Formamidopyrimidine Glycosylase
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins*
  • Genes, Bacterial
  • Guanine / analogs & derivatives
  • Guanine / metabolism
  • Guanine Nucleotides / metabolism*
  • Guanosine Triphosphate / metabolism
  • Molecular Sequence Data
  • N-Glycosyl Hydrolases / physiology
  • Oxidation-Reduction
  • Oxidative Stress / genetics*
  • Phosphoric Monoester Hydrolases / physiology
  • Point Mutation
  • Pyrophosphatases
  • Suppression, Genetic*
  • Templates, Genetic

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • Guanine Nucleotides
  • 8-hydroxyguanine
  • Guanine
  • Guanosine Triphosphate
  • 8-Hydroxy-2'-Deoxyguanosine
  • Phosphoric Monoester Hydrolases
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • mutY adenine glycosylase
  • DNA-Formamidopyrimidine Glycosylase
  • DNA-formamidopyrimidine glycosylase, E coli
  • Pyrophosphatases
  • mutT protein, E coli
  • Deoxyguanosine