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Schizosaccharomyces pombe Hsk1p is a potential cds1p target required for genome integrity.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2000 Nov; Vol. 20 (21), pp. 7922-32. - Publication Year :
- 2000
-
Abstract
- 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.
- Subjects :
- Alleles
Amino Acid Sequence
Bleomycin pharmacology
Cell Nucleus metabolism
Checkpoint Kinase 2
DNA Replication
Dose-Response Relationship, Radiation
Fluorescent Antibody Technique
Fungal Proteins biosynthesis
G1 Phase
Hydroxyurea pharmacology
Immunoblotting
Mitosis
Molecular Sequence Data
Phenotype
Phosphorylation
Precipitin Tests
Protein Kinases metabolism
S Phase drug effects
S Phase genetics
S Phase radiation effects
Sequence Homology, Amino Acid
Temperature
Time Factors
Ultraviolet Rays
Cell Cycle Proteins
Fungal Proteins genetics
Fungal Proteins physiology
Protein Serine-Threonine Kinases
Schizosaccharomyces chemistry
Schizosaccharomyces pombe Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 20
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 11027263
- Full Text :
- https://doi.org/10.1128/MCB.20.21.7922-7932.2000