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Published online July 30, 2007
doi:10.1083/jcb.200701163
The Journal of Cell Biology, Vol. 178, No. 3, 345-354
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Thein et al.
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Report

 Astrin is required for the maintenance of sister chromatid cohesion and centrosome integrity

Kerstin H. Thein, Julia Kleylein-Sohn, Erich A. Nigg, and Ulrike Gruneberg

Department of Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany

Correspondence to Ulrike Gruneberg: u.gruneberg{at}liv.ac.uk

Faithful chromosome segregation in mitosis requires the formation of a bipolar mitotic spindle with stably attached chromosomes. Once all of the chromosomes are aligned, the connection between the sister chromatids is severed by the cysteine protease separase. Separase also promotes centriole disengagement at the end of mitosis. Temporal coordination of these two activities with the rest of the cell cycle is required for the successful completion of mitosis. In this study, we report that depletion of the microtubule and kinetochore protein astrin results in checkpoint-arrested cells with multipolar spindles and separated sister chromatids, which is consistent with untimely separase activation. Supporting this idea, astrin-depleted cells contain active separase, and separase depletion suppresses the premature sister chromatid separation and centriole disengagement in these cells. We suggest that astrin contributes to the regulatory network that controls separase activity.

U. Gruneberg's present address is University of Liverpool Cancer Research Centre, Liverpool L3 9TA, UK.

Abbreviations used in this paper: CENP, centromere protein; Plk1, Pololike kinase 1; TOGp, tumor overexpressed gene protein.


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