Activation of the Ras/cyclic AMP pathway in the yeast Saccharomyces cerevisiae does not prevent G1 arrest in response to nitrogen starvation.
Cells carrying mutations that activate the Ras/cyclic AMP (Ras/cAMP) pathway fail to accumulate in G1 as unbudded cells and lose viability in response to nitrogen starvation. This observation has led to the idea that cells carrying this type of mutation are sensitive to nitrogen starvation because they are unable to appropriately arrest in G1. In this study, we tested predictions made by this model. We found that cells with activating Ras/cAMP pathway mutations do not continue to divide after nitrogen starvation, show a normal decrease in steady state levels of START-specific transcripts, and are not rescued by removal of cAMP during nitrogen starvation. These findings are inconsistent with the idea that activation of the Ras/cAMP pathway prevents growth arrest in cells starved for nitrogen. Our finding that cells with an active Ras/cAMP pathway have dramatically reduced amino acid stores suggests an alternative model. We propose that cells at high cAMP levels are unable to store sufficient nutrients to allow return to the G1 phase of the cell cycle when they are suddenly deprived of nitrogen. It is this inability to return to G1, rather than a failure to arrest, which leaves cells at different points in the cell cycle following nitrogen starvation.
Markwardt
D D
DD
School of Pharmacy, University of Wisconsin, Madison 53706, USA.
Garrett
J M
JM
Eberhardy
S
S
Heideman
W
W
D000596:Amino Acids / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D009154:Mutation; D009584:Nitrogen / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
D000596:Amino Acids; D012333:RNA, Messenger; D000242:Cyclic AMP; D018631:ras Proteins; D009584:Nitrogen