Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase.
Arrest of the cell cycle at the G2 checkpoint, induced by DNA damage, requires inhibitory phosphorylation of the kinase Cdc2 in both fission yeast and human cells. The kinase Wee1 and the phosphatase Cdc25, which regulate Cdc2 phosphorylation, were evaluated as targets of Chk1, a kinase essential for the checkpoint. Fission yeast cdc2-3w Deltacdc25 cells, which express activated Cdc2 and lack Cdc25, were responsive to Wee1 but insensitive to Chk1 and irradiation. Expression of large amounts of Chk1 produced the same phenotype as did loss of the cdc25 gene in cdc2-3w cells. Cdc25 associated with Chk1 in vivo and was phosphorylated when copurified in Chk1 complexes. These findings identify Cdc25, but not Wee1, as a target of the DNA damage checkpoint.
Furnari
B
B
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Rhind
N
N
Russell
P
P
D000251:Adenosine Triphosphatases / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D016195:G2 Phase; D005720:Gamma Rays; D005800:Genes, Fungal; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins; D015398:Signal Transduction; D013696:Temperature; D020666:ras-GRF1
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D020666:ras-GRF1; D019000:Phosphotyrosine; D011494:Protein Kinases; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe; D016203:CDC2 Protein Kinase; D000251:Adenosine Triphosphatases; C061897:Rad3 protein, S cerevisiae; D004265:DNA Helicases