Influence of S-adenosylmethionine pool size on spontaneous mutation, dam methylation, and cell growth of Escherichia coli

Escherichia coli strains that are deficient in the Ada and Ogt DNA repair m ethyltransferases display an elevated spontaneous G:C-to-A:T transition mut ation rate, and this increase has been attributed to mutagenic O-6-alkylgua nine lesions being formed via the alkylation of DNA by endogenous metabolit es. Here we test the frequently cited hypothesis that S-adenosylmethionine (SAM) can act as a weak alkylating agent in vivo and that it contributes to endogenous DNA alkylation. By regulating the expression of the rat liver S AM synthetase and the bacteriophage T3 SAM hydrolase proteins in E. coli, a 100-fold range of SAM levels could be achieved. However, neither increasin g nor decreasing SAM levels significantly affected spontaneous mutation rat es, leading us to conclude that SAM is not a major contributor to the endog enous formation of OG-methylguanine lesions in E. coli.