CDC25 MITOTIC INDUCER TARGETED BY CHK1 DNA-DAMAGE CHECKPOINT KINASE

Arrest of the cell cycle at the G(2) checkpoint, induced by DNA damage , requires inhibitory phosphorylation of the kinase Cdc2 in both fissi on yeast and human cells. The kinase Wee1 and the phosphatase Cdc25, w hich regulate Cdc2 phosphorylation, were evaluated as targets of Chk1, a kinase essential for the checkpoint. Fission yeast cdc2-3w Delta cd c25 cells, which express activated Cdc2 and lack Cdc25, were responsiv e 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 phos phorylated when copurified in Chk1 complexes. These findings identify Cdc25, but not Wee1, as a target of the DNA damage checkpoint.