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Vol. 13, No. 5, pp. 532-544, March 1, 1999
1 Department of Physiology, University of California, San
Francisco, California 94143-0444 USA; 2 European Molecular
Biology Laboratory, Heidelberg 69012 Germany
Chromosome segregation depends on kinetochores, the structures that
mediate chromosome attachment to the mitotic spindle. We isolated
mutants in IPL1, which encodes a protein kinase, in a screen
for budding yeast mutants that have defects in sister chromatid
separation and segregation. Cytological tests show that ipl1
mutants can separate sister chromatids but are defective in chromosome
segregation. Kinetochores assembled in extracts from ipl1
mutants show altered binding to microtubules. Ipl1p phosphorylates the
kinetochore component Ndc10p in vitro and we propose that Ipl1p
regulates kinetochore function via Ndc10p phosphorylation. Ipl1p
localizes to the mitotic spindle and its levels are regulated during
the cell cycle. This pattern of localization and regulation is similar
to that of Ipl1p homologs in higher eukaryotes, such as the human
aurora2 protein. Because aurora2 has been implicated in oncogenesis,
defects in kinetochore function may contribute to genetic instability
in human tumors.
[Key Words: sister chromatid separation; chromosome segregation; Ipl1p/aurora kinase; kinetochores; microtubules; yeast]
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