PMZ = Amphibian Nieuwkoop center

TLS Online TPP Program

#Id: 6008

#Unit 3. Fundamental Processes

At the end of the cell cycle, ORC is bound to A–B1 elements of the origin. There is a change during G1 that results from the binding of Cdc6 and Cdt1 proteins to the ORC. 

In yeast, Cdc6 is a highly unstable protein, with a half-life of 5 minutes. It is synthesized during G1 and typically binds to ORC between the exit from mitosis and late G1. Its rapid degradation means that no protein is available later in the cycle.

TLS Online TPP Program

#Id: 6009

#Unit 3. Fundamental Processes

TLS Online TPP Program

#Id: 6010

#Unit 3. Fundamental Processes

In mammalian cells, Cdc6 is controlled differently; it is phosphorylated during S phase, and as a result it is degraded by the ubiquitination pathway.  Cdt1 is initially stabilized by the protein Geminin, which prevents its degradation, and subsequent Geminin binding prevents its reuse

TLS Online TPP Program

#Id: 6011

#Unit 3. Fundamental Processes

Hence Cdc6 and Cdt1 are the key licensing factors and helicase loading proteins.

TLS Online TPP Program

#Id: 6012

#Unit 3. Fundamental Processes

Cdc6 has an ATPase activity that is required for it to support initiation.

TLS Online TPP Program

#Id: 6013

#Unit 3. Fundamental Processes

The presence of Cdc6 and Cdt1 at the yeast origin allows the MCM proteins to bind to the complex in G1 in the inactive state.