APC/C^Cdh1 specific degradation of Hsl1 and Clb2 is required for proper stress responses of S. cerevisiae

Cdh1 activates the Anaphase Promoting Complex/Cyclosome (APC/C ^Cdh1) throughout G₁ to degrade key cell cycle proteins. Cdh1 is not essential for cell proliferation, in spite of the fact that overexpression of some its degradation substrates is highly toxic. We report here that cdh1Δ cells are sensitive to stresses that activate the CWI (Cell Wall Integrity) and Hog1 MAP kinase pathways. Stresses did not activate APC/C^Cdh1 and cellular sensitivity was thus clearly due to constitutively elevated substrate levels. To explore the contribution of stabilization of individual APC/C^Cdh1 substrates to stress sensitivity, we generated cell lines expressing stabilized substrate mutants under their endogenous promoters. Cells expressing stabilized Hsl1 were sensitive to caffeine and failed to activate the Slt2 pathway. Cells expressing partially stable Clb2 were particularly sensitive to different stresses, possibly due to reduced Sic1 levels. Cells expressing stabilized Cdc5 were much less stress sensitive. Interestingly sensitivity of cdh1Δ cells does not seem to be restricted to G₁ but is manifested also during S and G₂ when the APC/C^Cdh1 is inactive anyway. We thus hypothesize that a role of G₁ specific APC/C^Cdh1 activity is to reset substrate levels to enables appropriate regulation of substrate accumulation in the subsequent phases of the cell cycle.