FIGURE 19-9 Regulation of cell cycle transitions. Cell cycle transitions are regulated by cyclin-CDK protein kinases, protein phosphatases, and ubiquitin-protein ligases. Here the cell cycle is diagrammed, with the major stages of mitosis shown at the top. In early G₁, no cyclin-CDKs are active. In mid-G₁, G₁/S phase CDKs activate transcription of genes required for DNA replication. S phase is initiated by the SCF ubiquitin-protein ligase, which ubiquitinylates inhibitors of S phase CDKs, marking them for degradation by proteasomes. The S phase CDKs then activate DNA replication, and DNA synthesis commences. Once DNA replication is complete, cells enter G₂. In late G₂, mitotic CDKs trigger entry into mitosis. During prophase, the nuclear envelope breaks down and chromosomes align on the mitotic spindle, but they cannot separate until the anaphase-promoting complex (APC/C), a ubiquitin-protein ligase, ubiquitinylates the anaphase inhibitor protein securin, marking it for degradation by proteasomes. This results in degradation of protein complexes linking the sister chromatids and the onset of anaphase as the sister chromatids separate. APC/C also ubiquitinylates mitotic cyclins, causing their degradation by proteasomes. The resulting drop in mitotic CDK activity, along with the action of protein phosphatases, results in chromosome decondensation, reassembly of nuclear membranes around the daughter-cell nuclei, and cytokinesis.