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 methyltransferases display an elevated spontaneous G:C-to-A:T transition mutation rate, and this increase has been attributed to mutagenic O(6)-alkylguanine lesions being formed via the alkylation of DNA by endogenous metabolites. 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 SAM synthetase and the bacteriophage T3 SAM hydrolase proteins in E. coli, a 100-fold range of SAM levels could be achieved. However, neither increasing nor decreasing SAM levels significantly affected spontaneous mutation rates, leading us to conclude that SAM is not a major contributor to the endogenous formation of O(6)-methylguanine lesions in E. coli.
Posnick
L M
LM
Division of Toxicology, Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Samson
L D
LD
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D019175:DNA Methylation; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D006867:Hydrolases / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008780:Methyltransferases; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism*; D014157:Transcription Factors
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D014157:Transcription Factors; D012436:S-Adenosylmethionine; D008780:Methyltransferases; C045675:Ada protein, E coli; D019853:O(6)-Methylguanine-DNA Methyltransferase; C067511:Ogt protein, E coli; D006867:Hydrolases; C019614:adenosylmethionine hydrolase