Induction of SOS and adaptive responses by alkylating agents in Escherichia coli mutants deficient in 3-methyladenine-DNA glycosylase activities.
The induction of SOS and adaptive responses by alkylating agents was studied in Escherichia coli mutants tagA and alkA deficient in 3-methyladenine-DNA glycosylase activities. The SOS response was measured using an sfiA::lacZ operon fusion. The sfiA operon, in the double mutant tagA alkA, is induced at 5-50-fold lower concentrations of all tested methylating and ethylating compounds, as compared to the wild-type strain. In all cases, the tagA mutation, which inactivates the constitutive and specific 3-alkyladenine-DNA glycosylase I (TagI), sensitizes the strain to the SOS response. The sensitization effect of alkA mutation, which inactivates the inducible 3-alkyladenine-DNA glycosylase II (TagII), is observed under conditions which allow the induction of the adaptive response. We conclude that the persistence of 3-methyladenine and 3-ethyladenine residues in DNA most likely leads to the induction of the SOS functions. In contrast, the adaptive response, evaluated by O6-methylguanine-DNA methyltransferase activity in cell extracts, was not affected by either tagA or alkA mutations. The results suggest that the SOS and adaptive responses use different alkylation products as an inducing "signal". However, adaptation protein TagII inhibits the induction of the SOS response to some extent, due to its action at the level of signal production. Finally, we provide conditions to improve short-term bacterial tests for the detection of genotoxic alkylating agents.
D000220:Adaptation, Biological / Q000187:drug effects*; D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D000477:Alkylating Agents / Q000494:pharmacology*; D045647:DNA Glycosylases; D004260:DNA Repair / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D008780:Methyltransferases / Q000378:metabolism; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000172:deficiency* / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013014:SOS Response, Genetics / Q000187:drug effects*; D001616:beta-Galactosidase / Q000378:metabolism
D000477:Alkylating Agents; C025946:3-methyladenine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D001616:beta-Galactosidase; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D000225:Adenine