Thymineless mutagenesis in bacteria.

Abstract

Experimental evidence indicates that while thymine starvation induces primarily A:T----G:C transitions in bacteria, it also may cause other uncharacterized base substitutions as well as frameshifts and deletions. However, models have been proposed to explain only the induction of point mutations by thymine deprivation. In this study, we demonstrate that thymine nucleotide depletion induces both point mutations in the his-4 and 1acI genes of Escherichia coli and reversion of the frameshift mutations trpE9777, trpA21, trpA540, and trpA9813. Analysis of the 1acI amber spectrum revealed that thymine starvation resulted in G:C----A:T transitions and all possible transversions. A defect in uracil-DNA glycosylase has little effect on the induction of 1acI- mutations but reduces substantially the induction of trpE9777 revertants. These data show that the mutagenic specificity of thymine nucleotide depletion is not limited to A:T----G:C transitions and suggest that removal of uracil from DNA plays a role in the generation of frameshift mutations by thymine deprivation. A model that involves nucleotide misincorporation into DNA and induction of error-prone repair functions in response to thymine starvation is proposed to account for these findings.