Cdc6

It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate S phase and mitosis.

CDC6 assembles after ORC in an ATP dependent manner and is required for loading MCM proteins onto the DNA.

[4] A near-atomic resolution model of the entire ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) complex with DNA was assembled from EM data in 2017.

[5] It is thought that the CDC6-Cdt1 complex uses ATP hydrolysis to thread DNA through the central hole of the MCM doughnut.

Nevertheless, it has been suggested that regulation of CDC6 is one of several redundant mechanisms that prevent re-replication of the DNA in eukaryotic cells.

The domains I and II form a cashew-shaped molecule that bind ATP in the cleft and additionally build the sensor motif for ATP/ADP recognition.

Cdc6 overexpression interferes with the expression of INK4/ARF tumor suppressor genes through a mechanism involving the epigenetic modification of chromatin at the INK4/ARF locus.

In addition, CDC6 overexpression in primary cells may promote DNA hyper-replication and induce a senescence response similar to that caused by oncogene activation.

Potential role of Cdc6 at the initiation of DNA replication. [ 3 ]
Crystal Structure of CDC6 from Pyrobaculum aerophilum. Domain I in green, domain II in blue and domain III in red. Beta-sheets are shown in orange.