Ubiquitin-Protein Ligases-

SCF- Degradation of phosphorylated Sic1

TLS Online TPP Program

#Id: 6017

#Unit 3. Fundamental Processes

In mammalian cells, Cdt1 is targeted for degradation by the action of a protein complex that is recruited to the origin of replication by PCNA, the eukaryotic counterpart of the bacterial b clamp.

TLS Online TPP Program

#Id: 6018

#Unit 3. Fundamental Processes

As the transition from G1 to S phase begins, CDK/cyclins recruit cdc45 and the GINS complex to the MCM helicase, which then becomes known as the CMG complex (Cdc45-MCM-GINS)

TLS Online TPP Program

#Id: 6019

#Unit 3. Fundamental Processes

TLS Online TPP Program

#Id: 6020

#Unit 3. Fundamental Processes

As cells enter into the S phase of the cell cycle, two kinases, CDK and DDK, are activated.  DDK phosphorylates loaded Mcm2-7 helicase, and CDK phosphorylates Sld2 and Sld3.Phosphorylated Sld2 and Sld3 bind to Dpb11, and together these proteins facilitate binding of the helicase-activating proteins, Cdc45 and GINS, to the helicase.  

TLS Online TPP Program

#Id: 6021

#Unit 3. Fundamental Processes

Cdc45 and GINS form a stable complex with the Mcm2-7 helicase (called the Cdc45/ Mcm2-7/GINS, or CMG, complex) and dramatically activate Mcm2-7 helicase activity.

TLS Online TPP Program

#Id: 6022

#Unit 3. Fundamental Processes

The leading-strand DNA polymerase (E) is recruited to the helicase at this stage (before DNA unwinding). After formation of the CMG complex, Sld2, Sld3, and Dpb11 are released from the origin.