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Chk1-Dependent Regulation of Cdc25B Functions to Coordinate Mitotic Events
Harald Löffler, Blanca Rebacz, Anthony D. Ho, Jiri Lukas, Jiri Bartek and Alwin Krämer
volume 5 | issue 21
1 november 2006Pages: 2543 - 2547
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The coordination of mitotic spindle formation and chromatin condensation is an essential prerequisite for successful mitosis. Both events are thought to be initiated by cyclin B/Cdk1, whose initial activation occurs in late prophase at the centrosomes. Recently, we have shown that Chk1 localizes to interphase centrosomes and thereby negatively regulates entry into mitosis by preventing premature activation of cyclin B/Cdk1. Here, we demonstrate that inhibition of Chk1 kinase induces mitotic entry with regular spindle assembly but aberrant and mislocalized chromatin. This effect, which we have termed the ‘paraspindle’ phenotype, was reverted by downregulation of Cdc25B phosphatase using siRNA, which restored normal mitosis with regular chromatin. Analogous to Chk1 inhibition, the ‘paraspindle’ phenotype was induced by overexpression of Cdc25B but not Cdc25A. Our results suggest that Chk1 functions to coordinate mitotic events through regulation of Cdc25B.
Authors
Harald Löffler
University of Heidelberg; Heidelberg, Germany
Blanca Rebacz
University of Heidelberg; Heidelberg, Germany
Anthony D. Ho
University of Heidelberg; Heidelberg, Germany
Jiri Lukas
Danish Cancer Society; Copenhagen, Denmark
Jiri Bartek
Danish Cancer Society; Copenhagen, Denmark
Alwin Krämer
University of Heidelberg; Heidelberg, Germany
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.