D-Type Cyclins and Their Cyclin-dependent Kinases: G1 Phase Integrators of the Mitogenic Response

The processes of DNA replication (S phase) and mitosis (M phase) must be properly coordinated to ensure that the complement of genetic material in the proliferating somatic cells of an organism remains constant. Genes that control the orderly progression of S phase to M phase are vital for cell division, and their encoded products likely represent the core building blocks of the cell cycle machinery. Examples of proteins that play roles in these processes include the p34cdc2/CDC28 protein kinase, its regulatory subunit cyclin B, and the kinases (e.g., wee1/mik1) and phosphatases (e.g., cdc25) that posttranslationally regulate p34cdc2/cyclin B kinase activity to control mitotic entry and exit in all eukaryotic cells (Norbury and Nurse 1992). Superimposed on the basic replicative and mitotic apparati are checkpoint controllers, which guarantee that an essential process is completed before another begins by resetting the cell cycle clock when certain conditions are improperly met (Hartwell and...