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.
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 RFC(Ctf18) replication factor C complex, and Chl1, a putative DNA helicase. We show ... that RFC(Ctf18) 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 it is required for the proper resumption of replication after fork arrest. We also show that chl1Delta is synthetically lethal with ctf18Delta and that a dosage increase of chl1(+) rescues sensitivities of swi1Delta 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 RFC(Ctf18) and the Swi1-Swi3 complex function in separate and redundant pathways essential for replication fork stabilization to facilitate sister chromatid cohesion in fission yeast.
Mesh Terms:
Alkylation, Carrier Proteins, Cell Cycle Proteins, Chromatin, DNA Damage, DNA Replication, DNA-Binding Proteins, Enzyme Activation, Hydroxyurea, Microbial Viability, Models, Biological, Mutation, Protein Binding, Protein Transport, Replication Protein C, S Phase, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sister Chromatid Exchange, Ultraviolet Rays
Alkylation, Carrier Proteins, Cell Cycle Proteins, Chromatin, DNA Damage, DNA Replication, DNA-Binding Proteins, Enzyme Activation, Hydroxyurea, Microbial Viability, Models, Biological, Mutation, Protein Binding, Protein Transport, Replication Protein C, S Phase, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sister Chromatid Exchange, Ultraviolet Rays
Mol. Biol. Cell
Date: Feb. 01, 2008
PubMed ID: 18045993
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