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Vol. 20, Issue 17, 3818-3827, September 1, 2009
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*Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;
Molecular and Cellular Biology Program, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA 98195; and
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8
Submitted April 27, 2009;
Revised June 25, 2009;
Accepted July 2, 2009
Monitoring Editor: Kerry S. Bloom
Accurate chromosome segregation depends on sister kinetochores making bioriented attachments to microtubules from opposite poles. An essential regulator of biorientation is the Ipl1/Aurora B protein kinase that destabilizes improper microtubule–kinetochore attachments. To identify additional biorientation pathways, we performed a systematic genetic analysis between the ipl1-321 allele and all nonessential budding yeast genes. One of the mutants, mcm21
, precociously separates pericentromeres and this is associated with a defect in the binding of the Scc2 cohesin-loading factor at the centromere. Strikingly, Mcm21 becomes essential for biorientation when Ipl1 function is reduced, and this appears to be related to its role in pericentromeric cohesion. When pericentromeres are artificially tethered, Mcm21 is no longer needed for biorientation despite decreased Ipl1 activity. Taken together, these data reveal a specific role for pericentromeric linkage in ensuring kinetochore biorientation.
Address correspondence to: Sue Biggins (sbiggins{at}fhcrc.org)
Abbreviations used: MT, microtubule; NC-Mcd1, noncleavable Mcd1; SGA, systematic genetic analysis.
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