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.
Ansbach
Alison B
AB
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Noguchi
Chiaki
C
Klansek
Ian W
IW
Heidlebaugh
Mike
M
Nakamura
Toru M
TM
Noguchi
Eishi
E
D000478:Alkylation / Q000187:drug effects / Q000528:radiation effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D006918:Hydroxyurea / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects / Q000528:radiation effects; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D051818:Replication Protein C / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects / Q000528:radiation effects; D012568:Schizosaccharomyces / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; C502679:Ctf18 protein, S pombe; D004268:DNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C499635:Swi3 protein, S pombe; C513096:swi1 protein, S pombe; D051818:Replication Protein C; D006918:Hydroxyurea