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Saccharomyces cerevisiae proteins Cdc4 and Cdc20 contain WD40 repeats and participate in proteolytic processes. However, they are thought to act at two different stages of the cell cycle: Cdc4 is involved in the proteolysis of the Cdk inhibitor, Sic1, necessary for G1 /S transition, while Cdc20 mediates anaphase-promoting complex-dependent degradation of anaphase inhibitor Pds1, a process necessary for the onset of chromosome segregation. We have isolated three mutant alleles ofCDC4 (cdc4-10 ,cdc4-11 , andcdc4-16 ) which suppress the nuclear division defect ofcdc20-1 cells. However, the previously characterized mutationcdc4-1 and a new allele,cdc4-12 , do not alleviate the defect ofcdc20-1 cells. This genetic interaction suggests an additional role for Cdc4 in G2 /M. Reexamination of thecdc4-1 mutant revealed that, in addition to being defective in the onset of S phase, it is also defective in G2 /M transition when released from hydroxyurea-induced S-phase arrest. A second function forCDC4 in late S or G2 phase was further confirmed by the observation that cells lacking theCDC4 gene are arrested both at G1 /S and at G2 /M. We subsequently isolated additional temperature-sensitive mutations in theCDC4 gene (such ascdc4-12 ) that render the mutant defective in both G1 /S and G2 /M transitions at the restrictive temperature. While the G1 /S block in bothcdc4-12 andcdc4 Δ mutants is abolished by the deletion of theSIC1 gene (causing the mutants to be arrested predominantly in G2 /M), the preanaphase arrest in thecdc4-12 mutant is relieved by the deletion ofPDS1 . Collectively, these observations suggest that, in addition to its involvement in the initiation of S phase, Cdc4 may also be required for the onset of anaphase.

Cdc4, a Protein Required for the Onset of S Phase, Serves an Essential Function during G2/M Transition in Saccharomyces cerevisiae

Cdc4, a Protein Required for the Onset of S Phase, Serves an Essential Function during G₂/M Transition in Saccharomyces cerevisiae