This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bayart, E. Articles by Amor-Guéret, M. Search for Related Content PubMed PubMed Citation Articles by Bayart, E. Articles by Amor-Guéret, M.

A Major Role for Mitotic cdc2 Kinase Inactivation in the Establishment of the Mitotic DNA Damage Checkpoint

¹ CNRS, UMR 8126 and ² CNRS, UMR 8125, Institut Gustave Roussy, Villejuif, France

Cdc2 kinase is inactivated when DNA damage occurs during the spindle assembly checkpoint. Here, we show that the level of mitotic Bloom syndrome protein phosphorylation reflects the level of cdc2 activity. A complete inactivation of cdc2 by either introduction of DNA double-strand breaks or roscovitine treatment prevents exit from mitosis. Thus, mitotic cdc2 inactivation plays a major role in the establishment of the mitotic DNA damage checkpoint. In response to mitotic cdc2 inactivation, the M/G₁ transition is delayed after releasing the drug block in nonmalignant cells, whereas tumor cells exit mitosis without dividing and rereplicate their DNA, which results in mitotic catastrophe. This opens the way for new chemotherapeutic strategies.

This article has been cited by other articles:

				L. Magnaghi-Jaulin, G. Eot-Houllier, G. Fulcrand, and C. Jaulin Histone Deacetylase Inhibitors Induce Premature Sister Chromatid Separation and Override the Mitotic Spindle Assembly Checkpoint Cancer Res., July 1, 2007; 67(13): 6360 - 6367. [Abstract] [Full Text] [PDF]

				G. I. Shapiro Cyclin-Dependent Kinase Pathways As Targets for Cancer Treatment J. Clin. Oncol., April 10, 2006; 24(11): 1770 - 1783. [Abstract] [Full Text] [PDF]