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Swi1 Prevents Replication Fork Collapse and Controls Checkpoint Kinase Cds1
Journal article   Open access   Peer reviewed

Swi1 Prevents Replication Fork Collapse and Controls Checkpoint Kinase Cds1

Eishi Noguchi, Chiaki Noguchi, Li-Lin Du and Paul Russell
Molecular and cellular biology, v 23(21), pp 7861-7874
Nov 2003
PMID: 14560029
url
https://doi.org/10.1128/MCB.23.21.7861-7874.2003View
Published, Version of Record (VoR) Open

Abstract

DNA Dynamics and Chromosome Structure
The replication checkpoint is a dedicated sensor-response system activated by impeded replication forks. It stabilizes stalled forks and arrests division, thereby preserving genome integrity and promoting cell survival. In budding yeast, Tof1 is thought to act as a specific mediator of the replication checkpoint signal that activates the effector kinase Rad53. Here we report studies of fission yeast Swi1, a Tof1-related protein required for a programmed fork-pausing event necessary for mating type switching. Our studies have shown that Swi1 is vital for proficient activation of the Rad53-like checkpoint kinase Cds1. Together they are required to prevent fork collapse in the ribosomal DNA repeats, and they also prevent irreversible fork arrest at a newly identified hydroxyurea pause site. Swi1 also has Cds1-independent functions. Rad22 DNA repair foci form during S phase in swi1 mutants and to a lesser extent in cds1 mutants, indicative of fork collapse. Mus81, a DNA endonuclease required for recovery from collapsed forks, is vital in swi1 but not cds1 mutants. Swi1 is recruited to chromatin during S phase. We propose that Swi1 stabilizes replication forks in a configuration that is recognized by replication checkpoint sensors.

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Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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