Effect of the methionine analogs, ethionine and norleucine, on DNA synthesis in Escherichia coli 15T −

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The effect of the methionine analogs, norleucine and ethionine, was studied in a mutant of Escherichia coli 15T − which requires thymine, arginine, tryptophan and methionine. There is a twofold increase in the total DNA content of the culture when either ethionine or norleucine is substituted for methionine. About half of this DNA is lost subsequently if glucose is the carbon source in the medium, whereas none is lost if either aspartate or succinate is the carbon source. No particular region of the bacterial chromosome is lost, such as the region synthesized after amino acid starvation or the portion made immediately after transfer to medium containing the methionine analog. Radioactive and density label experiments show that DNA cannot be replicated past the point on the chromosome first synthesized in the presence of ethionine. However, addition of methionine will allow replication of about 30% more of the DNA synthesized in the presence of the methionine analogs. It can be demonstrated that addition of methionine to the medium will result in the methylation of DNA synthesized previously in the presence of either methionine analog. It is hypothesized that non-methylated DNA cannot be used as a template for further DNA synthesis.