The CAK1 gene encodes the major CDK-activating kinase (CAK) in budding
yeast and is required for activation of Cdc28p for cell cycle progres
sion from G(2) to M phase. Here we describe the isolation of a mutant
allele of CAK1 in a synthetic lethal screen with the Sit4 protein phos
phatase. Analysis of several different cak1 mutants shows that althoug
h the G(2) to M transition appears most sensitive to loss of Cak1p fun
ction, Cak1p is also required for activation of Cdc28p for progression
from G(1) into S phase. Further characterization of these mutants sug
gests that, unlike the CAK identified from higher eukaryotes, Cak1p of
budding yeast may not play a role in general transcription. Finally,
although Cak1 protein levels and in vitro protein kinase activity do n
ot fluctuate during the cell cycle, at least a fraction of Cak1p assoc
iates with higher molecular weight proteins, which may be important fo
r its in vivo function.