Control of the cAMP Pathway by the Cell Cycle Start Function, CDC25, in Saccharomyces cerevisiae
Abstract
We investigated the relationship in Saccharomyces cerevisiae between the cell cycle start function, CDC25, and two mutants defining components of the cAMP pathway. The thermolabile adenylate cyclase mutant cyr1-2(ts) is phenotypically similar to the temperature-sensitive mutant cdc25(ts) in that both mutants, when shifted to the restrictive temperature, arrest in G1 of the cell cycle and permit the initiation of meiosis and sporulation. The mutant bcy1 [a lesion resulting in a low level of regulatory (R) subunit and a high level of active, catalytic (C) subunit of the CAMP-dependent protein kinase] suppresses the temperature-sensitive phenotype of cyr1-2(ts) and confers an asporogenous phenotype. We found that cdc25(ts) complemented cyr1-2(ts), and, unlike cyr1-2(ts), was not suppressible by bcy1, demonstrating that cyr1 and CDC25 must encode different functions. Also our results indicate that CDC25 does not encode the R subunit of the CAMP-dependent protein kinase. In addition, although the cdc25(ts) bcy1 double mutant was temperature sensitive like cdc25(ts), we found that the cdc25(ts) bcy1 homozygous diploid was asporogenous like bcy1/bcy1. The inability of the cdc25(ts)bcy1 double mutant to sporulate demonstrated that CDC25 does not encode the C subunit of the cAMP kinase, and indicated that the CDC25 function modulates the cAMP pathway to control meiosis and sporulation. Further, the temperature-sensitive phenotype of the double mutant, and hence the inability of bcy1 to suppress cdc25(ts), suggested that a second CDC25 cell cycle function exists which is independent of the cAMP pathway. Taken together, our genetic data indicated that the CDC25 protein has a dual regulatory role: (1) to control the decision between proliferation and differentiation by controlling the cAMP pathway; and (2) to control the cell cycle positively by a mechanism independent of the cAMP pathway. cdc25(ts) and cyr1-2(ts) conferred resistance to ammonium and methylamine. This suggests that CDC25 and the cAMP pathway work in concert as an ammonium signal-response system. We conclude that CDC25 controls meiosis and sporulation in response to nutritional stimuli by modulating the cAMP pathway.