DNA TOPOISOMERASE-I CONTROLS THE KINETICS OF PROMOTER ACTIVATION AND DNA TOPOLOGY IN SACCHAROMYCES-CEREVISIAE

Inactivation of the nonessential TOP1 gene, which codes for Saccharomy ces cerevisiae DNA topoisomerase I, affects the rate of transcription starting at the ADH2 promoter. For both the chromosomal gene and the p lasmid-borne promoter, mRNA accumulation is kinetically favored in the mutant relative to a wild-type isogenic strain. The addition of ethan ol causes in wild-type yeast strains a substantial increase in linking number both on the ADH2-containing plasmid and on the resident 2 mum DNA. Evidence has been obtained that such an in vivo increase in linki ng number depends on (i) the activity of DNA topoisomerase I and of no other enzyme and (ii) ethanol addition, not on the release from gluco se repression. A direct cause-effect relationship between the change i n supercoiling and alteration of transcription cannot be defined. Howe ver, the hypothesis that a metabolism-induced modification of DNA topo logy in a eukaryotic cell plays a role in regulating gene expression i s discussed.