Abstract
THE mutagenic lesion O6-methylguanine (O6-MeG) is slowly but actively removed from DNA in Escherichia coli cells treated with alkylating agents1. In bacteria exposed to sublethal concentrations of chemical mutagens such as N-methyl-Nā²-nitro-N-nitrosoguanidine (MNNG) or N- methyl -N-nitrosourea (MNUA), an apparently error-free repair system is induced that confers increased resistance to the mutagenic and lethal effects of challenge doses of the same or related compounds2ā4. This adaptive response is associated with an increased ability of the induced E. coli to remove 06-MeG residues from their DNA (see ref. 5 and preceding paper6). We have investigated the action of cell-free extracts from adapted E. coli on DNA containing O6-MeG residues. Here we report that O6-MeG disappears from alkylated DNA after incubation with a crude enzyme fraction from adapted cells, although no concomitant release of the methyl group or the alkylated base or nucleotide occurs. Instead, this process is due to a previously unrecognised DNA repair mechanism involving enzyme-catalysed structural alteration of the alkylated residue.
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KARRAN, P., LINDAHL, T. & GRIFFIN, B. Adaptive response to alkylating agents involves alteration in situ of O6-methylguanine residues in DNA. Nature 280, 76ā77 (1979). https://doi.org/10.1038/280076a0
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DOI: https://doi.org/10.1038/280076a0
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