The conditions required for the induction of petite yeast mutants by fluorinated pyrimidines

Abstract

Cytoplasmic petite mutagenesis by 5-fluorouracil (5FU) was prevented by temperature sensitive mutations which blocked either nuclear transcription or cytoplasmic translation. However, 5FU was also ineffective in resting cells and in cells exposed to α-mating factor, showing that cell division or nuclear DNA synthesis is required for the mutagenic event to take place. In addition, the mutagenic effect of 5FU was completely prevented by daunomycin, and since this agent preferentially inhibits respiratory growth and was shown to selectively block RNA synthesis in the mitochondria, it was concluded that petite mutagenesis resulted from incorporation of 5FU into mitochondrial RNA. Since inhibition of mitochondrial protein synthesis by erythromycin had little immediate effect on the mutagenicity of 5FU, it was deduced that the RNA in question is not directly involved in mitochondrial translation, and may have a regulatory function.