Slk19 clusters kinetochores and facilitates chromosome bipolar attachment

Mol Biol Cell. 2013 Mar;24(5):566-77. doi: 10.1091/mbc.E12-07-0552. Epub 2013 Jan 2.

Abstract

In all eukaryotic cells, DNA is packaged into multiple chromosomes that are linked to microtubules through a large protein complex called a kinetochore. Previous data show that the kinetochores are clustered together during most of the cell cycle, but the mechanism and the biological significance of kinetochore clustering are unknown. As a kinetochore protein in budding yeast, the role of Slk19 in the stability of the anaphase spindle has been well studied, but its function in chromosome segregation has remained elusive. Here we show that Slk19 is required for kinetochore clustering when yeast cells are treated with the microtubule-depolymerizing agent nocodazole. We further find that slk19Δ mutant cells exhibit delayed kinetochore capture and chromosome bipolar attachment after the disruption of the kinetochore-microtubule interaction by nocodazole, which is likely attributed to defective kinetochore clustering. In addition, we show that Slk19 interacts with itself, suggesting that the dimerization of Slk19 may mediate the interaction between kinetochores for clustering. Therefore Slk19 likely acts as kinetochore glue that clusters kinetochores to facilitate efficient and faithful chromosome segregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase / genetics
  • Chromosome Segregation / drug effects
  • Chromosome Segregation / genetics*
  • Chromosomes / genetics
  • Chromosomes / ultrastructure
  • DNA / drug effects
  • DNA / genetics*
  • Kinetochores / drug effects
  • Kinetochores / ultrastructure
  • Microtubule-Associated Proteins / genetics*
  • Microtubules / drug effects
  • Microtubules / genetics
  • Mitosis / genetics
  • Mutation
  • Nocodazole / pharmacology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / genetics

Substances

  • Microtubule-Associated Proteins
  • Saccharomyces cerevisiae Proteins
  • Slk19 protein, S cerevisiae
  • DNA
  • Nocodazole