A novel mutator of Escherichia coli carrying a defect in the dgt gene, encoding a dGTP triphosphohydrolase.
A novel mutator locus in Escherichia coli was identified from a collection of random transposon insertion mutants. Several mutators in this collection were found to have an insertion in the dgt gene, encoding a previously characterized dGTP triphosphohydrolase. The mutator activity of the dgt mutants displays an unusual specificity. Among the six possible base pair substitutions in a lacZ reversion system, the G.C-->C.G transversion and A.T-->G.C transition are strongly enhanced (10- to 50-fold), while a modest effect (two- to threefold) is also observed for the G.C-->A.T transition. Interestingly, a two- to threefold reduction in mutant frequency (antimutator effect) is observed for the G.C-->T.A transversion. In the absence of DNA mismatch repair (mutL) some of these effects are reduced or abolished, while other effects remain unchanged. Analysis of these effects, combined with the DNA sequence contexts in which the reversions take place, suggests that alterations of the dGTP pools as well as alterations in the level of some modified dNTP derivatives could affect the fidelity of in vivo DNA replication and, hence, account for the overall mutator effects.
Gawel
Damian
D
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA.
Hamilton
Michael D
MD
Schaaper
Roel M
RM
D002876:Chromosomes, Bacterial / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism
D004251:DNA Transposable Elements; C094399:DinB protein, E coli; D029968:Escherichia coli Proteins; D011938:Rec A Recombinases; D010744:Phosphoric Monoester Hydrolases
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