The transition from the G1 to S phase is controlled by the Cyclin E:Cdk2 complexes. As the Cyclin E:Cdk2 complexes are formed, the Cdk2 is phosphorylated by the Wee1 and Myt1 kinases. This phosphorylation keeps the Cdk2 inactive. In yeast this control is called the cell size checkpoint control. The dephosphorylation of the Cdk2 by Cdc25A activates the Cdk2, and is coordinated with the cells reaching the proper size, and with the DNA synthesis machinery being ready. The Cdk2 then phosphorylates G1/S specific proteins, including proteins required for DNA replication initiation. The beginning of S-phase is marked by the first nucleotide being laid down on the primer during DNA replication at the early-firing origins.Failure to appropriately regulate cyclin E accumulation can lead to accelerated S phase entry, genetic instability, and tumorigenesis. The amount of
cyclin E protein in the cell is controlled by ubiquitin-mediated proteolysis (see Woo, 2003).This pathway has not yet been annotated in Reactome.