ACTIVATION OF THE RAS CYCLIC AMP PATHWAY IN THE YEAST SACCHAROMYCES-CEREVISIAE DOES NOT PREVENT G(1) ARREST IN RESPONSE TO NITROGEN STARVATION/

Cells carrying mutations that activate the Ras/cyclic AMP (Ras/cAMP) p athway fail to accumulate in G(1) as unbudded cells and lose viability in response to nitrogen starvation, This observation has led to the i dea that cells carrying this type of mutation are sensitive to nitroge n starvation because they are unable to appropriately arrest in G(1). In this study, we tested predictions made by this model. We found that cells with activating Ras/cAMP pathway mutations do not continue to d ivide after nitrogen starvation, show a normal decrease in steady stat e levels of START-specific transcripts, and are not rescued by removal of cAMP during nitrogen starvation, These findings are inconsistent w ith the idea that activation of the Ras/cAMP pathway prevents growth a rrest in cells starved for nitrogen. Our finding that cells with an ac tive Ras/cAMP pathway have dramatically reduced amino acid stores sugg ests an alternative model. We propose that cells at high cAMP levels a re unable to store sufficient nutrients to allow return to the G(1) ph ase of the cell cycle when they are suddenly deprived of nitrogen, It is this inability to return to G(1), rather than a failure to arrest, which leaves cells at different points in the cell cycle following nit rogen starvation.