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Science 5 September 1997:
Vol. 277. no. 5331, pp. 1495 - 1497
DOI: 10.1126/science.277.5331.1495
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Reports

Cdc25 Mitotic Inducer Targeted by Chk1 DNA Damage Checkpoint Kinase

Beth Furnari, Nicholas Rhind, Paul Russell *

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 Delta cdc25 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.

Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
*   To whom correspondence should be addressed. E-mail: prussell{at}scripps.edu.

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   Abstract »    Full Text »    PDF »
Cyclin B-dependent kinase and caspase-1 activation precedes mitochondrial dysfunction in fumarylacetoacetate-induced apoptosis.
R. JORQUERA and R. M. TANGUAY (1999)
FASEB J 13, 2284-2298
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