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

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 isy1Δ syf2Δ shows a temperature‐dependent cell cycle arrest. This arrest is due to lower levels of α‐tubulin, a protein encoded by TUB1 and TUB3, two intron‐containing genes. We show that the low levels of α‐tubulin in isy1Δ syf2Δ 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.