Figure 1.

Cdks are regulated by tyrosine phosphorylation and control pre-RC assembly and firing. Cdk activity plays opposing roles in controlling DNA replication at different times in the cell cycle, both inhibiting pre-RC assembly and triggering origin firing, leading to bidirectional replication fork movement. Cdk1 activity requires binding to cyclin and is regulated by the opposing activities of Cdc25 phosphatase and Wee1 kinase, which phosphorylates a tyrosine in the Cdk1 active site that inhibits ATP binding.