Schizosaccharomyces pombe Hsk1p is a potential cds1p target required for genome integrity.

The fission yeast Hsk1p kinase is an essential activator of DNA replication. Here we report the isolation and characterization of a novel mutant allele of the gene. Consistent with its role in the initiation of DNA synthesis, hsk1(ts) genetically interacts with several S-phase mutants. At the restrictive temperature, hsk1(ts) cells ...
suffer abnormal S phase and loss of nuclear integrity and are sensitive to both DNA-damaging agents and replication arrest. Interestingly, hsk1(ts) mutants released to the restrictive temperature after early S-phase arrest in hydroxyurea (HU) are able to complete bulk DNA synthesis but they nevertheless undergo an abnormal mitosis. These findings indicate a second role for hsk1 subsequent to HU arrest. Consistent with a later S-phase role, hsk1(ts) is synthetically lethal with Deltarqh1 (RecQ helicase) or rad21ts (cohesin) mutants and suppressed by Deltacds1 (RAD53 kinase) mutants. We demonstrate that Hsk1p undergoes Cds1p-dependent phosphorylation in response to HU and that it is a direct substrate of purified Cds1p kinase in vitro. These results indicate that the Hsk1p kinase is a potential target of Cds1p regulation and that its activity is required after replication initiation for normal mitosis.
Mesh Terms:
Alleles, Amino Acid Sequence, Bleomycin, Cell Cycle Proteins, Cell Nucleus, DNA Replication, Dose-Response Relationship, Radiation, Fluorescent Antibody Technique, Fungal Proteins, G1 Phase, Hydroxyurea, Immunoblotting, Mitosis, Molecular Sequence Data, Phenotype, Phosphorylation, Precipitin Tests, Protein Kinases, Protein-Serine-Threonine Kinases, S Phase, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sequence Homology, Amino Acid, Temperature, Time Factors, Ultraviolet Rays
Mol. Cell. Biol.
Date: Nov. 01, 2000
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