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MBC in Press, published online ahead of print November 28, 2007
Mol. Biol. Cell 10.1091/mbc.E07-06-0618

A more recent version of this article appeared on February 1, 2008
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Submitted on June 28, 2007
Revised on November 9, 2007
Accepted on November 19, 2007

RFCCtf18 and the Swi1-Swi3 Complex Function in Separate and Redundant Pathways Required for the Stabilization of Replication Forks to Facilitate Sister Chromatid Cohesion in Schizosaccharomyces pombe

Alison B. Ansbach,* Chiaki Noguchi,* Ian W. Klansek,* Mike Heidlebaugh,* Toru M. Nakamura,{dagger} and Eishi Noguchi*

*Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102; {dagger}Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607

Monitoring Editor: Mark Solomon

Sister chromatid cohesion is established during S-phase near the replication fork. However, how DNA replication is coordinated with chromosomal cohesion pathway is largely unknown. Here we report studies of fission yeast Ctf18, a subunit of the RFCCtf18 replication factor C complex, and Chl1, a putative DNA helicase. We show that RFCCtf18 is essential in the absence of the Swi1-Swi3 replication fork protection complex required for the S-phase stress response. Loss of Ctf18 leads to an increased sensitivity to S-phase stressing agents, a decreased level of Cds1 kinase activity, and accumulation of DNA damage during S-phase. Ctf18 associates with chromatin during S-phase and is required for the proper resumption of replication after fork arrest. We also show that chl1{Delta} is synthetically lethal with ctf18{Delta} and that a dosage increase of chl1+ rescues sensitivities of swi1{Delta} to S-phase stressing agents, indicating that Chl1 is involved in the S-phase stress response. Finally, we demonstrate that inactivation of Ctf18, Chl1 or Swi1-Swi3 leads to defective centromere cohesion, suggesting the role of these proteins in chromosome segregation. We propose that RFCCtf18 and the Swi1-Swi3 complex function in separate and redundant pathways essential for replication fork stabilization to facilitate sister chromatid cohesion in fission yeast.

Address correspondence to: Eishi Noguchi (enoguchi{at}drexelmed.edu)






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