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A more recent version of this article appeared on September 1, 2003
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Submitted on December 31, 2002
Accepted on May 15, 2003
1 Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
2 MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, Du Cane Road, LondonW12 ONN, UK
* Corresponding author. E-mail address: brandeis\{at}cc.huji.ac.il.
Human HT2-19 cells with a conditional cdk1 mutation stop dividing upon cdk1 inactivation and undergo multiple rounds of endoreplication. We show here that major cell cycle events remain synchronized in these endoreplicating cells. DNA replication alternates with gap phases and cell cycle specific cyclin E expression is maintained. Centrosomes duplicate in synchrony with chromosome replication giving rise to polyploid cells with multiple centrosomes. Centrosome migration, a typical prophase event, also takes place in endoreplicating cells. The timing of these events is unaffected by cdk1 inactivation as compared with normally dividing cells. Nuclear lamina breakdown, in contrast, previously shown to be dependent on cdk1, does not take place in endoreplicating HT2-19 cells. Moreover, breakdown of all other major components of the nuclear lamina, like the inner nuclear membrane proteins and nuclear pore complexes, seem also to depend on cdk1. Interestingly, the APC/C ubiquitin ligase is activated in these endoreplicating cells by fzr but not by fzy. The oscillations of interphase events are thus independent of cdk1 and of mitosis but may depend on APC/Cfzr activity.
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