Tension between two kinetochores suffices for their bi-orientation on the mitotic spindle

Nature. 2004 Mar 4;428(6978):93-7. doi: 10.1038/nature02328. Epub 2004 Feb 11.

Abstract

The movement of sister chromatids to opposite spindle poles during anaphase depends on the prior capture of sister kinetochores by microtubules with opposing orientations (amphitelic attachment or bi-orientation). In addition to proteins necessary for the kinetochore-microtubule attachment, bi-orientation requires the Ipl1 (Aurora B in animal cells) protein kinase and tethering of sister chromatids by cohesin. Syntelic attachments, in which sister kinetochores attach to microtubules with the same orientation, must be either 'avoided' or 'corrected'. Avoidance might be facilitated by the juxtaposition of sister kinetochores such that they face in opposite directions; kinetochore geometry is therefore deemed important. Error correction, by contrast, is thought to stem from the stabilization of kinetochore-spindle pole connections by tension in microtubules, kinetochores, or the surrounding chromatin arising from amphitelic but not syntelic attachment. The tension model predicts that any type of connection between two kinetochores suffices for efficient bi-orientation. Here we show that the two kinetochores of engineered, unreplicated dicentric chromosomes in Saccharomyces cerevisiae bi-orient efficiently, implying that sister kinetochore geometry is dispensable for bi-orientation. We also show that Ipl1 facilitates bi-orientation by promoting the turnover of kinetochore-spindle pole connections in a tension-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase
  • Aurora Kinases
  • Chromatids / metabolism
  • Chromosome Segregation
  • Chromosomes, Fungal / metabolism
  • DNA Replication
  • Intracellular Signaling Peptides and Proteins
  • Kinetics
  • Kinetochores / metabolism*
  • Microtubules / metabolism
  • Mitosis
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Spindle Apparatus / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • Aurora Kinases
  • IPL1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases