Nature Cell Biology 8, 78 - 83 (2005)
Published online: 4 December 2005; | doi:10.1038/ncb1341
The Ipl1-Aurora protein kinase activates the spindle checkpoint by creating unattached kinetochoresBenjamin A. Pinsky1, Charles Kung2, Kevan M. Shokat2, 3
& Sue Biggins11
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., PO Box 19024, Seattle, WA 98109, USA. 2
Department of Cellular and Molecular Pharmacology, Box 2280, University of California at San Francisco, San Francisco, CA 94143, USA. 3
Department of Chemistry, University of California at Berkeley, Berkeley, CA 94720, USA.
Correspondence should be addressed to Sue Biggins sbiggins@fhcrc.org The spindle checkpoint ensures accurate chromosome segregation by delaying cell-cycle progression until all sister kinetochores capture microtubules from opposite poles and come under tension (for reviews, see refs 1, 2). Although the checkpoint is activated by either the lack of kinetochore-microtubule attachments or defects in the tension exerted by microtubule-generated forces, it is not clear whether these signals are linked. We investigated the connection between tension and attachment by studying the conserved budding yeast Ipl1Aurora protein kinase that is required for checkpoint activation in the absence of tension but not attachment3. Here, we show that spindle-checkpoint activation in kinetochore mutants that seem to have unattached kinetochores depends on Ipl1 activity. When Ipl1 function was impaired in these kinetochore mutants, the attachments were restored and the checkpoint was turned off. These data indicate that Ipl1 activates the checkpoint in response to tension defects by creating unattached kinetochores. Moreover, although the Dam1 kinetochore complex has been implicated as a key downstream target, we found the existence of unidentified Ipl1 sites on Dam1 or additional important substrates that regulate both microtuble detachment and the checkpoint.
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