Regulation of DNA replication during a cell cycle. At the end of the mitosis and G1, Geminin is degraded, and Cdt1 and Cdc6 recruit
MCM2–7 to ORC-bound origins to establish the pre-RC complex. At the onset of S-phase, CDKs and Cdc7/Dbf4 kinase (DDK) establish the pre-IC
complex by recruiting Cdc45 and the GINS complex to MCM2–7. With Cdc45 and GINS as accessory factors, MCM2–7 unwinds DNA, followed by
recruitment of replication machinery to start DNA replication. As MCM2–7 moves away from origins, pre-RCs are disassembled. In S and G2,
Geminin is expressed to inhibit Cdt1 activity and Cdt1 is also subject to proteasomal degradation, while Cdc6 is exported to cytoplasm. These
mechanisms prevent reassembly of pre-RC complex on already fired origins and subsequent re-replication within one cell cycle.