Cyclin D1 is degraded at the restriction point

The mammalian cell cycle is governed by Cyclin-Dependent Kinases (CDKs) whose activities are restricted by the availability of their cyclins. Temporal control of cyclin levels, therefore, lies at the very core of cell-cycle regulation. While cyclins E, A, and B are well understood, the dynamic regulation of Cyclin D remains elusive. Using live-cell imaging and single-cell tracking, we report here that Cyclin D1 levels drop upon passage through the Restriction Point (R-point) in G1, stay low in early S phase, and rise again in late S and G2. We show that Cyclin D1 is continuously synthesized and degraded throughout the cell cycle, with degradation and synthesis rates varying substantially across cell-cycle phases. The G1 drop in Cyclin D1 levels is caused by a sudden increase in the degradation rate. Our findings thus fill a crucial gap in the core cell-cycle control network.