CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both
exhibit genetic and physical ties to replication fork constituents. We find
that absence of either CTF4 or CTF18 causes sister chromatid cohesion fail
ure and leads to a preanaphase accumulation of cells that depends on the sp
indle assembly checkpoint. The physical and genetic interactions between CT
F4, CTF18, and core components of replication fork complexes observed in th
is study and others suggest that both gene products act in association with
the replication fork to facilitate sister chromatid cohesion. We find that
Ctf18p, an RFC1-like protein, directly interacts with Rfc2p, Rfc3p, Rfc4p,
and Rfc5p. However, Ctf18p is not a component of biochemically purified pr
oliferating cell nuclear antigen loading RF-C, suggesting the presence of a
discrete complex containing Ctf18p, Rfc2p, Rfc3p, Rfc4p, and Rfc5p. Recent
identification and characterization of the budding yeast polymerase kappa,
encoded by TRF4, strongly supports a hypothesis that the DNA. replication
machinery is required for proper sister chromatid cohesion. Analogous to th
e polymerase switching role of the bacterial and human RF-C complexes, we p
ropose that budding yeast RF-C-CTF18 may be involved in a polymerase switch
event that facilities sister chromatid cohesion. The requirement for CTF4
and CTF18 in robust cohesion identifies novel roles for replication accesso
ry proteins in this process.