PMID:12531387
| Citation |
Fowler, RG, White, SJ, Koyama, C, Moore, SC, Dunn, RL and Schaaper, RM (2003) Interactions among the Escherichia coli mutT, mutM, and mutY damage prevention pathways. DNA Repair (Amst.) 2:159-73 |
|---|---|
| Abstract |
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. |
| Links | |
| Keywords |
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 |
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