Cyclin-dependent kinase-dependent initiation of chromosomal DNA replication

Cyclin-dependent kinase (CDK) is essential for the initiation of chromosomal DNA replication. CDK phosphorylates two yeast replication proteins, SId2 and SId3, both of which bind to another replication protein, Dpb11 when phosphorylated. These interactions are essential and are the minimal requirements for CDK activation of chromosomal DNA replication. This review discusses how these phosphorylation-dependent interactions initiate DNA replication through the formation of the pre-loading complex (pre-LC) and its interaction with phosphorylated SId3 on replication origins. These steps are further regulated by multisite phosphorylation of SId2. SId3, on the other hand, must be turned over to reassociate with origins. Pol epsilon functions as a component of the pre-LC as well as a replicative DNA polymerase at replication forks.