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Eukaryotic DNA replication initiates in a two-step fashion (Diffley, 2004), and both steps are tightly regulated by phosphorylation and dephosphorylation of replication-initiation proteins. First, a multi-protein complex known as pre-RC (pre-replicative complex) is assembled on replication origins from late M to early G1 phase; this process is referred to as replication licensing. Subsequently, origin activation (firing) occurs in accordance to the rise of S-CDK (cyclin dependent kinase) and DDK (Dbf4p dependent kinase) activities during which replication forks are established and DNA synthesis begins.

Cell Cycle Control of DNA Replication by Phosphorylation and Dephosphorylation of Replication-Initiation Proteins in Budding Yeast