Fus3p and Kss1p control G1 arrest in Saccharomyces cerevisiae through a balance of distinct arrest and proliferative functions that operate in parallel with Far1p

In Saccharomyces cerevisiae, mating pheromones activate two MAP kinases (MA PKs), Fus3p and Kss1p, to induce G1 arrest prior to mating. Fus3p is known to promote G1 arrest by activating Far1p, which inhibits three Clnp/Cdc28p kinases. To analyze the contribution of Fus3p and Kss1p to G1 arrest that i s independent of Far1p, we constructed farl CLN strains that undergo G1 arr est from increased activation of the mating MAP kinase pathway. We find tha t Fus3p and Kss1p both control G1 arrest through multiple functions that op erate in parallel with Far1p. Fus3p and Kss1p together promote G1 arrest by repressing transcription of G1/S cyclin genes (CLN1, CLN2, CLB5) by a mech anism that blocks their activation by Cln3p/Cdc28p kinase. In addition, Fus 3p and Kss1p counteract GI arrest through overlapping and distinct function s. Fus3p and Kss1p together increase the expression of CLN3 and PCL2 genes that promote budding, and Kss1p inhibits the MAP kinase cascade. Strikingly , Fus3p promotes proliferation by a novel function that is not linked to re duced Ste12p activity or increased levels of Cln2p/Cdc28p kinase. Genetic a nalysis suggests that Fus3p promotes proliferation through activation of Mc m1p transcription factor that upregulates numerous genes in G1 phase. Thus, Fus3p and Kss1p control G1 arrest through a balance of arrest functions th at inhibit the Cdc28p machinery and proliferative functions that bypass thi s inhibition.