FIGURE 19-12 Control of the G₁–S phase transition. (a) In budding yeast, Cln3-CDK activity rises during G₁ and is controlled by nutrient availability. Once sufficiently active, the kinase phosphorylates the transcriptional repressor Whi5, promoting its export from the nucleus. This causes the transcription factor complex SBF to induce the transcription of the G₁/S phase cyclin genes CLN1 and CLN2 and of other genes whose products are needed for DNA replication. G₁/S phase CDKs further phosphorylate Whi5, promoting further CLN1 and CLN2 transcription. Once sufficiently high levels of G₁/S phase CDKs have been produced, START is traversed. Cells enter the cell cycle: they initiate DNA replication, bud formation, and spindle pole body duplication. (b) In vertebrates, G₁ CDK activity rises during G₁ and is stimulated by the presence of growth factors. When signaling from growth factors is sustained, the resulting cyclin D–CDK4/6 complexes begin phosphorylating Rb, releasing some E2F, which stimulates transcription of the genes encoding cyclin E, CDK2, and E2F itself. The cyclin E–CDK2 complexes further phosphorylate Rb, resulting in a positive feedback loop that leads to a rapid rise in the expression and activity of both E2F and cyclin E–CDK2. Once G₁/S phase CDKs are sufficiently high, cells pass through the restriction point. They commence DNA replication and centrosome duplication.