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During the late M to the Gl phase of the cell cycle, the origin recognition complex ( ORC) binds to the replication origin,leading to the assembly of the pre-replicative complex for subsequent initiation of eukaryotic chromosome replication. We found that the cell cycle-dependent phosphorylation of human Orc2,one of the six subunits of ORC,dissociates ORC from chromatin and replication origins.Phosphorylation at Thr-116 and Thr-226 0f Orc2 0ccurs by cyclin-dependent kinase( CDK) during the S phase and is maintained until the M phase.Protein phosphatase I (PPI) dephosphorylates phosphorylated Orc2 to promote the binding of the ORC to chromatin and replication origins for the subsequent round of the cell cycle.The binding of PPI to Orc2 and the dephosphorylation of phosphorylated Orc2 by PPI occurred in a cell cycle-dependent manner.