Blocking CHK1 Expression Induces Apoptosis and Abrogates the G2 Checkpoint Mechanism
Checkpoint kinase 1 (Chki) 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 report that blocking Chki expression by antisense or ribozymes in mammalian cell...
| Main Authors: | , , , , , , , , |
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| 格式: | Article |
| 語言: | English |
| 出版: |
Elsevier
2001-01-01
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| 叢編: | Neoplasia: An International Journal for Oncology Research |
| 主題: | |
| 在線閱讀: | http://www.sciencedirect.com/science/article/pii/S1476558601800543 |
| 總結: | Checkpoint kinase 1 (Chki) 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 report that blocking Chki expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chki inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chki is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response. |
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| ISSN: | 1476-5586 1522-8002 |