Abstract
The resistance of Escherichia coli to simple alkylating agents, for example N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), is markedly increased in cells previously exposed to low doses of the agents. This adaptive response seems to reflect improved repair of alkylation lesions in DNA, and cells become less sensitive to both the mutagenic and killing effects of alkylating agents1,2. Adaptation to the former is due largely to the induction of a repair function that removes O6-methylguanine (m6G) from DNA3,4. This activity has been purified from induced cells and is attributed to a protein that transfers the methyl group of an m6G residue in DNA to one of its own cysteine residues5. Consequently, no excision of damaged nucleotide residues seems to be necessary. The adaptive response to killing by alkylating agents, however, is less understood. DNA excision–repair with gap-filling catalysed by DNA polymerase I seems to occur as part of the inducible response, as it depends on the presence of a functional polA+ gene2 and enhanced DNA polymerase I-mediated repair synthesis has been observed in adapted cells challenged with MNNG6. Here we show that the adaptive response involves induction of not only a methyltransferase for m6G, but also a DNA glycosylase that catalyses the release of purines methylated at ring nitrogen atoms. We also identify the minor alkylation product 3-methyl-guanine (m3G) as an important lethal lesion.
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Karran, P., Hjelmgren, T. & Lindahl, T. Induction of a DNA glycosylase for N-methylated purines is part of the adaptive response to alkylating agents. Nature 296, 770–773 (1982). https://doi.org/10.1038/296770a0
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DOI: https://doi.org/10.1038/296770a0
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