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A number of lines of evidence have suggested a possible involvement of the mitosis-promoting protein kinase Cdc2 in the process of apoptotic cell death, and one recent study concluded that premature activation of Cdc2 is required for apoptosis. Here we have used a temperature-sensitive murine Cdc2 mutant cell line and Cdc2 inhibitor compounds to study the effect of inhibition of this protein kinase on apoptosis induced by DNA-damaging drugs. Inhibition of Cdc2 activity before or during exposure to DNA strand break-inducing drugs had the effect of increasing the level of subsequent apoptosis, as assessed by electron microscopy and flow cytometry. We conclude that, far from being required for cell death, a form of mammalian Cdc2 suppresses apoptosis induced by DNA damage. This form of Cdc2 appears to be active in G2-arrested cells and is therefore presumably distinct from the mitosis-promoting Cdc2-cyclin B heterodimer.

Type

Journal article

Journal

J Cell Sci

Publication Date

08/1995

Volume

108 ( Pt 8)

Pages

2897 - 2904

Keywords

Animals, Antineoplastic Agents, Apoptosis, CDC2 Protein Kinase, Cell Cycle, Cell Death, Cell Nucleus, DNA Damage, Female, Flow Cytometry, HL-60 Cells, Humans, Mammary Neoplasms, Experimental, Mice, Microscopy, Electron, Mitoxantrone, Models, Biological, Tumor Cells, Cultured