Efficient duplication of the genome requires the concerted action of helicase 
and DNA polymerases at replication forks to avoid stalling of the replication 
machinery and consequent genomic instability. In eukaryotes, the physical 
coupling between helicase and DNA polymerases remains poorly understood. Here we 
define the molecular mechanism by which the yeast Ctf4 protein links the 
Cdc45-MCM-GINS (CMG) DNA helicase to DNA polymerase α (Pol α) within the 
replisome. We use X-ray crystallography and electron microscopy to show that 
Ctf4 self-associates in a constitutive disk-shaped trimer. Trimerization depends 
on a β-propeller domain in the carboxy-terminal half of the protein, which is 
fused to a helical extension that protrudes from one face of the trimeric disk. 
Critically, Pol α and the CMG helicase share a common mechanism of interaction 
with Ctf4. We show that the amino-terminal tails of the catalytic subunit of Pol 
α and the Sld5 subunit of GINS contain a conserved Ctf4-binding motif that docks 
onto the exposed helical extension of a Ctf4 protomer within the trimer. 
Accordingly, we demonstrate that one Ctf4 trimer can support binding of up to 
three partner proteins, including the simultaneous association with both Pol α 
and GINS. Our findings indicate that Ctf4 can couple two molecules of Pol α to 
one CMG helicase within the replisome, providing a new model for lagging-strand 
synthesis in eukaryotes that resembles the emerging model for the simpler 
replisome of Escherichia coli. The ability of Ctf4 to act as a platform for 
multivalent interactions illustrates a mechanism for the concurrent recruitment 
of factors that act together at the fork.