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Downloaded from genesdev.cshlp.org on November 11, 2021 - Published by Cold Spring Harbor Laboratory Press Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress 1 2 2,3 1,4 Mihoko Kai, Michael N. Boddy, Paul Russell, and Teresa S.-F. Wang 1 2 Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA; Department of Molecular Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA The replication checkpoint kinase Cds1 preserves genome integrity by stabilizing stalled replication forks. Cds1 targets substrates through its FHA domain. The Cds1 FHA domain interacts with Mus81, a subunit of the Mus81–Eme1 structure-specific endonuclease. We report here that Mus81 and Rhp51 are required for generating deletion mutations in fission yeast replication mutants that experience replication stress. A mutation in the Mus81 FHA-binding motif eliminates its Cds1-binding and Cds1-dependent phosphorylation. Furthermore, this mutation exacerbates the deletion mutator phenotype of a replication mutant, and induces a hyper-recombination phenotype in hydroxyurea-treated cells. In unperturbed cells, Mus81 associates with chromatin throughout S phase. In replication mutants grown at semipermissive temperature, Mus81 undergoes minor Cds1-dependent phosphorylation, remains chromatin-associated, generates deletion mutations, and maintains cell growth. Upon S-phase arrest by
Genes & Development – Unpaywall
Published: Apr 1, 2005
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