The dissimiliar mutational consequences of SN1 and SN2 DNA alkylation pathways: clues from the mutational specificity of dimethylsuiphate in the lacl gene of Escherichia coli

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Abstract
The mutational specificity of the monofunctional alkylating agent dimethylsulphate has been determined through the DNA sequence characterization of 121 lacI−d mutations of Escherichia coli. The predominant mutation induced was the G:C → A:T transition (75%). Transversions constituted 20% of all mutation with the greatest contribution being that of G:C → T:A events (12%). Runs of G:C base pairs were the preferred sites of frameshift mutation. One 6-bp sequence (5′-CCCGCG-3′) appeared to be highly susceptible to all classes of mutation and events within this sequence accounted for 33% of all mutations characterized. Although the distribution of G:C → A:T mutations appeared non-random, the site-specificity observed was quite different from that reported for SN1 alkylating agents. The results of this study highlight the differences between the consequences of SN1 and SN2 alkylation pathways.