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

被引:56
作者
Ansbach, Alison B. [1 ]
Noguchi, Chiaki [1 ]
Klansek, Ian W. [1 ]
Heidlebaugh, Mike [1 ]
Nakamura, Toru M. [2 ]
Noguchi, Eishi [1 ]
机构
[1] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA
[2] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA
关键词
D O I
10.1091/mbc.E07-06-0618
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 it 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.
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收藏
页码:595 / 607
页数:13
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