Figure 1: Assembly of the pre-replicative complex (pre-RC) 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. Upon passage to the S phase, 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 by the recruitment of Cdc45 and GINS to the pre-RC. Initiation of DNA synthesis occurs when replication protein A (RPA) and DNA polymerase α- primase, are recruited to the unwound replication origin.