Cyclin-dependent kinase and initiation at eukaryotic origins: a replication switch?

A growing body of evidence indicates that cyclin-dependent kinases (CDKs) regulate the activity of eukaryotic origins of replication both positively and negatively. Although the details of this control remain unclear, recent work suggests that CDKs act directly at origins, where they associate with and phosphorylate several key initiator proteins. These data suggest that a CDK-regulated replication switch operates at each origin to ensure that initiation occurs precisely once per cell cycle.