Finishing the cell cycle

The eukaryotic cell division cycle consists of two characteristic states: G 1, when replication origins of chromosomes are in a pre-replicative state, and S/G2/M, when they are in a post-replicative state (Nasmyth, 1995). Usin g straightforward biochemical kinetics, we show that these two states can b e created by antagonistic interactions between cyclin-dependent kinases (Cd k) and their foes: the cyclin-degradation machinery (APC) and a stoichiomet ric inhibitor (CKI). Irreversible transitions between these two self-mainta ining steady states drive progress through the cell cycle: at "Start" a cel l leaves the G1 state and commences chromosome replication, and at "Finish" the cell separates the products of replication to the incipient daughter c ells and re-enters G1. We propose that a protein-phosphatase, by up-regulat ing the APC and by stabilizing the CKI, plays an essential role at Finish. The phosphatase acts in parallel pathways; hence, cells can leave mitosis i n the absence of cyclin degradation or in the absence of the CKI. (C) 1999 Academic Press.