The role of cdc25 in checkpoints and feedback controls in the eukaryotic cell cycle

Major checkpoints that gate progression through the cell cycle function at the G1/S transition, entry into mitosis and exit from mitosis. Cells use feedback mechanisms to inhibit passage through these checkpoints in response to growth control signals, incomplete DNA replication or spindle assembly. In many organisms, transition points seem to involve regulation of the activity of cyclin-dependent kinases (cdks) not only through their interactions with various cyclins, but also by phosphorylation-dephosphorylation cycles acting on the kinase activity of the cdks. These phosphorylation cycles are modulated by the regulation of the opposing kinases and phosphatases that act on cdks and form feedback loops. In this article, we discuss the role of positive and negative feedback loops in cell cycle timing and checkpoints, focusing more specifically on the regulation of the dual specificity cdc25 phosphatase.