Rad51-dependent aberrant chromosome structures at telomeres and ribosomal DNA activate the spindle assembly checkpoint

Mol Cell Biol. 2014 Apr;34(8):1389-97. doi: 10.1128/MCB.01704-13. Epub 2014 Jan 27.

Abstract

The spindle assembly checkpoint (SAC) monitors defects in kinetochore-microtubule attachment or lack of tension at kinetochores and arrests cells at prometaphase. In fission yeast, the double mutant between pot1Δ and the helicase-dead point mutant of the RecQ helicase Rqh1 gene (rqh1-hd) accumulates Rad51-dependent recombination intermediates at telomeres and enters mitosis with those intermediates. Here, we found that SAC-dependent prometaphase arrest occurred more frequently in pot1Δ rqh1-hd double mutants than in rqh1-hd single mutants. SAC-dependent prometaphase arrest also occurred more frequently in rqh1-hd single mutants after cells were released from DNA replication block compared to the rqh1-hd single mutant in the absence of exogenous insult to the DNA. In both cases, Mad2 foci persisted longer than usual at kinetochores, suggesting a defect in kinetochore-microtubule attachment. In pot1Δ rqh1-hd double mutants and rqh1-hd single mutants released from DNA replication block, SAC-dependent prometaphase arrest was suppressed by the removal of the recombination or replication intermediates. Our results indicate that the accumulation of recombination or replication intermediates induces SAC-dependent prometaphase arrest, possibly by affecting kinetochore-microtubule attachment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Chromosome Segregation / genetics
  • Chromosomes, Fungal / genetics
  • DNA Repair / genetics
  • DNA, Ribosomal / genetics*
  • Genes, cdc / genetics*
  • Kinetochores / metabolism
  • M Phase Cell Cycle Checkpoints / genetics
  • Mitosis / genetics
  • Mitosis / physiology
  • Mutation / genetics
  • Rad51 Recombinase / genetics*
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins / genetics*
  • Schizosaccharomyces pombe Proteins / metabolism
  • Spindle Apparatus / genetics*
  • Telomere / genetics*

Substances

  • Cell Cycle Proteins
  • DNA, Ribosomal
  • Schizosaccharomyces pombe Proteins
  • Rad51 Recombinase