DISTINCT ROLES FOR CYCLIN-DEPENDENT KINASES IN CELL-CYCLE CONTROL

The key cell-cycle regulator Cdc2 belongs to a family of cyclin-depend ent kinases in higher eukaryotes. Dominant-negative mutations were use d to address the requirement for kinases of this family in progression through the human cell cycle. A dominant-negative Cdc2 mutant arreste d cells at the G2 to M phase transition, whereas mutants of the cyclin -dependent kinases Cdk2 and Cdk3 caused a G1 block. The mutant phenoty pes were specifically rescued by the corresponding wild-type kinases. These data reveal that Cdk3, in addition to Cdc2 and Cdk2, executes a distinct and essential function in the mammalian cell cycle.