FIGURE 19-14 Control of S phase onset in S. cerevisiae by regulated proteolysis of the S phase inhibitor Sic1. The S phase cyclin-CDK complexes begin to accumulate in G₁, but are inhibited by Sic1. This inhibition prevents initiation of DNA replication until the cells have completed all G₁ events. G₁/S phase CDKs assembled in late G₁ phosphorylate Sic1 at multiple sites step 1, marking it for ubiquitinylation by the SCF ubiquitin-protein ligase and subsequent proteasomal degradation step 2. The active S phase CDKs then trigger initiation of DNA synthesis step 3 by phosphorylating and recruiting MCM helicase activators to DNA replication origins. See R. W. King et al., 1996, Science 274:1652.