Blocking CHK1 expression induces apoptosis and abrogates the G2 checkpointmechanism

Checkpoint kinase 1 (Chk1) is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We repor t that blocking Chk1 expression by antisense or ribozymes in mammalian cell s induces apoptosis and interferes with the G2/M arrest induced by adriamyc in. The Chk1 inhibitor UCN-01 also blocks the G2 arrest after DNA damage an d renders cells more susceptible to adriamycin. These results indicate that Chk1 is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.