Origin recognition complex

ORC or Origin Recognition Complex is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes in an ATP-dependent manner to origins of replication.

During the G1 phase of the cell cycle, when S-phase CDK levels are low, ORC recruits Cdc6 and Cdt1.

One Cdc6 and one Cdt1 bind to each strand of DNA. Cdc6 and Cdt1 interact with each other and inhibit Mcm, a DNA helicase that binds after Cdc6 and Cdt1 binding to the ORC.

The ORC, Cdc6, Cdt1 and Mcm proteins form the Pre-replication complex.

Activated S-CDK triggers S-phase and phosphorylates Cdc6.

Phosphorylated Cdc6 is degraded.

Cdt1 is inhibited by geminin.

With Cdc6 and Cdt1 no longer bound, Mcm can unwind the double stranded DNA allowing the preinitiation complex to bind.

ORC is phosphorylated and DNA replication takes place.

DDK also participates in ORC activation and triggers the transition into DNA replication.