Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis

PLoS Genet. 2007 Nov;3(11):e213. doi: 10.1371/journal.pgen.0030213. Epub 2007 Oct 15.

Abstract

During cell division all chromosomes must be segregated accurately to each daughter cell. Errors in this process give rise to aneuploidy, which leads to birth defects and is implicated in cancer progression. The spindle checkpoint is a surveillance mechanism that ensures high fidelity of chromosome segregation by inhibiting anaphase until all kinetochores have established bipolar attachments to spindle microtubules. Bub1 kinase is a core component of the spindle checkpoint, and cells lacking Bub1 fail to arrest in response to microtubule drugs and precociously segregate their DNA. The mitotic role(s) of Bub1 kinase activity remain elusive, and it is controversial whether this C-terminal domain of Bub1p is required for spindle checkpoint arrest. Here we make a detailed analysis of budding yeast cells lacking the kinase domain (bub1DeltaK). We show that despite being able to arrest in response to microtubule depolymerisation and kinetochore-microtubule attachment defects, bub1DeltaK cells are sensitive to microtubule drugs. This is because bub1DeltaK cells display significant chromosome mis-segregation upon release from nocodazole arrest. bub1DeltaK cells mislocalise Sgo1p, and we demonstrate that both the Bub1 kinase domain and Sgo1p are required for accurate chromosome biorientation after nocodazole treatment. We propose that Bub1 kinase and Sgo1p act together to ensure efficient biorientation of sister chromatids during mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Positioning* / drug effects
  • Chromosome Segregation / drug effects
  • Chromosomes, Fungal / metabolism
  • Kinetochores / drug effects
  • Kinetochores / metabolism
  • Microbial Viability / drug effects
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Mitosis* / drug effects
  • Mutation
  • Nocodazole / pharmacology
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary
  • Protein Transport / drug effects
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomycetales / cytology*
  • Saccharomycetales / drug effects
  • Saccharomycetales / enzymology*
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / metabolism
  • Tubulin Modulators / pharmacology

Substances

  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Sgo1 protein, S cerevisiae
  • Tubulin Modulators
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases
  • Nocodazole