Fission yeast chk1 protein kinase links the rad checkpoint pathway to cdc2.
The dependence of cell-cycle progression on the integrity of the genome has been described as checkpoint control. A number of mutants of the fission yeast Schizosaccharomyces pombe, selected for their sensitivity to DNA damage caused by radiation (rad mutants) or to the DNA synthesis inhibitor hydroxyurea (hus mutants) have been classified as checkpoint mutants because they fail to arrest the cell cycle in response to DNA damage or incompletely replicated DNA. Coupling of the checkpoint pathways that monitor DNA repair and replication to control of the cell cycle is essential. In a search for components that interact with the cell-cycle regulatory kinase p34cdc2, we have identified a novel fission yeast protein kinase homologue which is involved in cell-cycle arrest when DNA damage has occurred or when unligated DNA is present. We have called the gene encoding this protein chk1 for checkpoint kinase. Multiple copies of chk1 partially rescue the ultraviolet sensitivity of rad1-1, a mutant deficient in checkpoint control. Identification of a gene involved in checkpoint control as a rescue of a cdc2 mutant links the rad1-dependent DNA-damage-sensing pathway and p34cdc2 activity.
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
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Walworth
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Davey
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Beach
D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics*; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D004271:DNA, Fungal / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D006918:Hydroxyurea / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D012568:Schizosaccharomyces / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe; D016203:CDC2 Protein Kinase; D004720:Endonucleases; C499354:rad1 protein, S pombe; D006918:Hydroxyurea