Telomere-nuclear envelope dissociation promoted by Rap1 phosphorylation ensures faithful chromosome segregation

Curr Biol. 2012 Oct 23;22(20):1932-7. doi: 10.1016/j.cub.2012.08.019. Epub 2012 Sep 6.

Abstract

Efficient chromosomal movements are important for the fidelity of chromosome segregation during mitosis; however, movements are constrained during interphase by tethering of multiple domains to the nuclear envelope (NE). Higher eukaryotes undergo open mitosis accompanied by NE breakdown, enabling chromosomes to be released from the NE, whereas lower eukaryotes undergo closed mitosis, in which NE breakdown does not occur. Although the chromosomal movements in closed mitosis are thought to be restricted compared to open mitosis, the cells overcome this problem by an unknown mechanism that enables accurate chromosome segregation. Here, we report the spatiotemporal regulation of telomeres in Schizosaccharomyces pombe closed mitosis. We found that the telomeres, tethered to the NE during interphase, are transiently dissociated from the NE during mitosis. This dissociation from the NE is essential for accurate chromosome segregation because forced telomere tethering to the NE causes frequent chromosome loss. The phosphorylation of the telomere protein Rap1 during mitosis, primarily by Cdc2, impedes the interaction between Rap1 and Bqt4, a nuclear membrane protein, thereby inducing telomere dissociation from the NE. We propose that the telomere dissociation from the NE promoted by Rap1 phosphorylation is critical for the fidelity of chromosome segregation in closed mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC2 Protein Kinase / metabolism
  • Cell Cycle / genetics
  • Chromosome Segregation / physiology*
  • Mitosis
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism*
  • Phosphorylation
  • Protein Structure, Tertiary
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Shelterin Complex
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Telomere / metabolism*
  • Telomere-Binding Proteins / metabolism*

Substances

  • Rap1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Shelterin Complex
  • Telomere-Binding Proteins
  • CDC2 Protein Kinase
  • cdc2 protein, S pombe