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Fig. 1. Assembly of the pre-replicative complex renders chromatin competent for replication. In early G1 phase, the origin recognition complex (ORC) recruits Cdc6, which in turn promotes loading of MCM proteins onto chromatin. Activation of the Cdc7/Dbf4 kinase and S phase-promoting cyclin-dependent kinases (CDKs) induces a conformational change in the MCM complex that is required for unwinding of origin DNA and recruits Cdc45 to the pre-RC. Initiation of DNA replication occurs when replication protein A (RPA) and DNA polymerase {alpha}-primase are recruited to the unwound replication origin.