Interactions among the Escherichia coli mutT, mutM, and mutY damage prevention pathways

DNA Repair (Amst). 2003 Feb 3;2(2):159-73. doi: 10.1016/s1568-7864(02)00193-3.


We have investigated in detail the interactions between the Escherichia coli mutT, mutM, and mutY error-prevention systems. Jointly, these systems protect the cell against the effects of the oxidative stress product, 8-oxoguanine (8-oxoG), a base analog with ambiguous base-pairing properties, pairing with either A or C during DNA synthesis. mutT mutator strains display a specific increase in A.T-->C.G transversions, while mutM and mutY mutator strains show specific G.C-->T.A increases. To study in more detail the in vivo processing of the various mutational intermediates leading to A.T-->C.G and G.C-->T.A transversions, we analyzed defined A.T-->C.G and G.C-->T.A events in strains containing all possible combinations of these mutator alleles. We report three major findings. First, we do not find evidence that the mutT allele significantly increases G.C-->T.A transversions in either mut(+), mutM, mutY or mutMmutY backgrounds. We interpret this result to indicate that incorporation of 8-oxodGTP opposite template C may not be frequent relative to incorporation opposite template A. Second, we show that mutT-induced A.T-->C.G transversions are significantly reduced in strains carrying mutY and mutMmutY deficiencies suggesting that 8-oxoG, when present in DNA, preferentially mispairs with dATP. Third, the mutY and mutMmutY deficiencies also decrease A.T-->C.G transversions in the mutT(+) background, suggesting that, even in the presence of functional MutT protein, A.T-->C.G transversions may still result from 8-oxodGTP misincorporation.

MeSH terms

  • DNA Glycosylases*
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA-Formamidopyrimidine Glycosylase
  • Drug Resistance, Bacterial / genetics
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Lac Operon / genetics
  • N-Glycosyl Hydrolases / genetics
  • N-Glycosyl Hydrolases / metabolism*
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Pyrophosphatases


  • Escherichia coli Proteins
  • Phosphoric Monoester Hydrolases
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • mutY adenine glycosylase
  • DNA-Formamidopyrimidine Glycosylase
  • DNA-formamidopyrimidine glycosylase, E coli
  • Pyrophosphatases
  • mutT protein, E coli