CDC45

Cdc45, or cell division control protein 45, is a conserved eukaryotic protein that plays a central role in DNA replication. It is a core component of the CMG helicase complex, which also includes Cdc45, MCM2-7, and the GINS complex. The CMG complex acts as the active helicase at replication forks, unwinding DNA to allow replication machinery to synthesize new strands.

In initiation, Cdc45 is recruited to licensed replication origins in a process that depends on cell cycle–regulated kinase activities. Activation of the MCM2-7 helicase by DDK (Dbf4-dependent kinase) and S-phase CDKs promotes the assembly of the CMG complex, incorporating Cdc45 and GINS. Once formed, the CMG helicase proceeds with fork unwinding and coordinates with DNA polymerases to drive replication elongation. Cdc45 physically interacts with MCM2-7 and GINS, stabilizing the active helicase and facilitating replisome progression.

Regulation of Cdc45 function occurs through phosphorylation and protein–protein interactions mediated by cell cycle cues, ensuring replication initiates at the appropriate time and proceeds in a controlled manner. The protein is essential for origin firing and efficient fork progression; loss or dysfunction of Cdc45 leads to replication stress and severe cell cycle defects.

Cdc45 is present across diverse eukaryotes and serves as a key link between replication licensing and replisome activation. It is a focus of study in basic cell biology and cancer research due to its crucial role in maintaining genome stability during DNA replication.