The ORC remains associated with a replication origin throughout the cell cycle. In early G1, Cdc6 associates with ORC. Aided by Cdc6, Mcm ring complexes then assemble on the adjacent DNA, resulting in the formation of the pre-replicative complex. The S-Cdk (with assistance from another protein kinase, not shown) then triggers origin firing, assembling DNA polymerase and other replication proteins and activating the Mcm protein rings to migrate along DNA strands as DNA helicases. The S-Cdk also blocks rereplication by causing the dissociation of Cdc6 from origins, its degradation, and the export of all excess Mcm out of the nucleus. Cdc6 and Mcm cannot return to reset an ORC-containing origin for another round of DNA replication until M-Cdk has been inactivated at the end of mitosis (see text).
