Chromosome transmission fidelity 4 (Ctf4) is a conserved protein required for 
DNA replication. In this report, interactions between human Ctf4 (hCtf4) and the 
replicative helicase containing the cell division cycle 45 
(Cdc45)/minichromosome maintenance 2-7 (Mcm2-7)/Go, Ichi, Nii, and San (GINS) 
(CMG) proteins [human CMG (hCMG) complex] were examined. The hCtf4-CMG complex 
was isolated following in vitro interaction of purified proteins (hCtf4 plus the 
hCMG complex), coinfection of Spodoptera frugiperda (Sf9) insect cells with 
viruses expressing the hCMG complex and hCtf4, and from HeLa cell chromatin 
after benzonase and immunoprecipitation steps. The stability of the hCtf4-CMG 
complex depends upon interactions between hCtf4 and multiple components of the 
hCMG complex. The hCtf4-CMG complex, like the hCMG complex, contains DNA 
helicase activity that is more salt-resistant than the helicase activity of the 
hCMG complex. We demonstrate that the hCtf4-CMG complex contains a homodimeric 
hCtf4 and a monomeric hCMG complex and suggest that the homodimeric hCtf4 acts 
as a platform linking polymerase α to the hCMG complex. The role of the hCMG 
complex as the core of the replisome is also discussed.