Biochemistry of cell cycle checkpoints at the G2/M and metaphase/anaphase transitions

Entry into mitosis is a highly regulated process essential for transmission of genetic information to the next generation. Biochemically, in fission yeast and higher eukaryotes, the decision to enter mitosis is mediated by checkpoints that regulate the tyrosine 15 phosphorylation state of Cdc2. The Wee1/mik1 tyrosine kinases and the Cdc25 phosphatase are the enzymes responsible for the phosphorylation/dephosphorylation of tyrosine 15, respectively, and both are also controlled by phosphorylation. In the case of Cdc25, Cdc2-dependent phosphorylation is activating and forms a positive feedback loop, whereas phosphorylation of Wee1 by other kinases is inhibitory. Evidence suggests that periodic changes in both protein phosphatase 1 and 2A also contribute to changes in Wee1 and Cdc25 activity during the cell cycle. Exit from mitosis is also a highly regulated process with potential checkpoint controls. The metaphase arrest of vertebrate eggs in Meiosis II by the mos protooncogene product is an apparent consequence of the ability of mos to phosphorylate and activate MAP kinase kinase and may involve cooperation with Cdk2/cyclin E.