CHANGES IN GENE-EXPRESSION IN THE RAS ADENYLATE-CYCLASE SYSTEM OF SACCHAROMYCES-CEREVISIAE - CORRELATION WITH CAMP LEVELS AND GROWTH ARREST

Levels of cyclic 3',5'-cyclic monophosphate (cAMP) play an important r ole in the decision to enter the mitotic cycle in the yeast, Saccharom yces cerevisiae. In addition to growth arrest at stationary phase, S. cerevisiae transiently arrest growth as they shift from fermentative t o oxidative metabolism (the diauxic shift). Experiments examining the role of cAMP in growth arrest at the diauxic shift show the following: 1) yeast lower cAMP levels as they exhaust their glucose supply and s hift to oxidative metabolism of ethanol, 2) a reduction in cAMP is ess ential for traversing the diauxic shift, 3) the decrease in adenylate cyclase activity is associated with a decrease in the expression of CY R1 and CDC25, two positive regulators of cAMP levels and an increase i n the expression of IRA1 and IRA2, two negative regulators of intracel lular cAMP, 4) mutants carrying disruptions in IRA1 and IRA2 were unab le to arrest cell division at the diauxic shift and were unable to pro gress into the oxidative phase of growth. These results indicate that changes cAMP levels are important in regulation of growth arrest at th e diauxic shift and that changes in gene expression plays a role in th e regulation of the Ras/adenylate cyclase system.