Mutations in genes of Saccharomyces cerevisiae encoding pre-mRNA splicing factors cause cell cycle arrest through activation of the spindle checkpoint

Nucleic Acids Res. 2002 Oct 15;30(20):4361-70. doi: 10.1093/nar/gkf563.


Previous work has identified a group of genes whose products play important roles in two seemingly unrelated processes: cell cycle progression and splicing. The products of these genes show a network of physical and genetic interactions suggestive of the existence of a protein complex, the cell cycle and splicing complex (CSC). Here we analyze the genetic interactions between ISY1, SYF2 and NTC20, three non-essential components of the CSC. We show that mutations in ISY1 cause lethality in the absence of Ntc20p, and that the double mutant isy1Delta syf2Delta shows a temperature-dependent cell cycle arrest. This arrest is due to lower levels of alpha-tubulin, a protein encoded by TUB1 and TUB3, two intron-containing genes. We show that the low levels of alpha-tubulin in isy1Delta syf2Delta trigger activation of the spindle checkpoint, causing cell cycle arrest. Thus, our results have uncovered an unexpected role for pre-mRNA splicing in the maintenance of the fidelity of chromosome transmission during cell division.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / genetics
  • Genes, Fungal
  • Microtubules / drug effects
  • Mutation
  • Nocodazole / pharmacology
  • Phenotype
  • RNA Precursors / metabolism*
  • RNA Splicing Factors
  • RNA Splicing*
  • RNA, Fungal / metabolism*
  • RNA-Binding Proteins / genetics
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure
  • Temperature
  • Tubulin / biosynthesis
  • Tubulin / genetics


  • CDC40 protein, S cerevisiae
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • RNA Precursors
  • RNA Splicing Factors
  • RNA, Fungal
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Tubulin
  • Nocodazole