SCFMet30-mediated control of the transcriptional activator Met4 is required for the G(1)-S transition

Progression through the cell cycle requires the coordination of basal metab olism with the cell cycle and growth machinery, Repression of the sulfur ge ne network is mediated by the ubiquitin ligase SCFMet30, which targets the transcription factor Met4p for degradation. Met30p is an essential protein in yeast. We have found that a met4 Delta met30 Delta double mutant is viab le, suggesting that the essential function of Met30p is to control Met4p, I n support of this hypothesis, a Met4p mutant unable to activate transcripti on does not cause inviability in a met30 Delta strain. Also, overexpression of an unregulated Met4p mutant is lethal in wild-type cells. Under non-per missive conditions, conditional met30 Delta strains arrest as large, unbudd ed cells with 1N DNA content, at or shortly after the pheromone arrest poin t, met30 Delta conditional mutants fail to accumulate CLN1 and CLN2, but no t CLN3 mRNAs, even when CLN1 and CLN2 are expressed from strong heterologou s promoters, One or more genes under the regulation of Met4p may delay the progression from G(1) into S phase through specific regulation of critical G(1) phase mRNAs.