The eukaryotic cell cycle comprises an ordered series of events orchestrated by cyclin-dependent kinases (Cdks), with unidirectional cell-cycle transitions being required for its successful completion. Proteolytic degradation of cyclins has been assumed to be responsible for the irreversible transitions, but here it is shown that, although forced cyclin degradation can drive mitotic exit, the re-synthesis of cyclin means that this is not sufficient for irreversibility. Rather, mitotic exit only become irreversible after activation of a double-negative feedback loop.
- Sandra López-Avilés
- Orsolya Kapuy
- Frank Uhlmann