Chemical genetics reveals a role for Mps1 kinase in kinetochore attachment during mitosis

Michele H. Jones, Brenda J. Huneycutt, Chad G. Pearson, Chao Zhang, Garry Morgan, Kevan Shokat, Kerry Bloom, Mark Winey

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Abstract

Accurate chromosome segregation depends on proper assembly and function of the kinetochore and the mitotic spindle. In the budding yeast, Saccharomyces cerevisiae, the highly conserved protein kinase Mps1 has well-characterized roles in spindle pole body (SPB, yeast centrosome equivalent) duplication and the mitotic checkpoint [1]. However, an additional role for Mps1 is suggested by phenotypes of MPS1 mutations that include genetic interactions with kinetochore mutations and meiotic chromosome segregation defects [1] and also by the localization of Mps1 at the kinetochore, the latter being independent of checkpoint activation [2]. We have developed a new MPS1 allele, mps1-as1, that renders the kinase specifically sensitive to a cell-permeable ATP analog inhibitor, allowing us to perform high-resolution execution point experiments that identify a novel role for Mps1 subsequent to SPB duplication. We demonstrate, by using both fixed- and live-cell fluoresence techniques, that cells lacking Mps1 function show severe defects in mitotic spindle formation, sister kinetochore positioning at metaphase, and chromosome segregation during anaphase. Taken together, our experiments are consistent with an important role for Mps1 at the kinetochore in mitotic spindle assembly and function.

Original languageEnglish (US)
Pages (from-to)160-165
Number of pages6
JournalCurrent Biology
Volume15
Issue number2
DOIs
StatePublished - Jan 26 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Jones, M. H., Huneycutt, B. J., Pearson, C. G., Zhang, C., Morgan, G., Shokat, K., Bloom, K., & Winey, M. (2005). Chemical genetics reveals a role for Mps1 kinase in kinetochore attachment during mitosis. Current Biology, 15(2), 160-165. https://doi.org/10.1016/j.cub.2005.01.010