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

Orna Dahan, Martin Kupiec

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4361-4370
Number of pages10
JournalNucleic Acids Research
Volume30
Issue number20
DOIs
StatePublished - 15 Oct 2002

Funding

FundersFunder number
Constantiner Institute for Molecular Genetics
Israel Cancer Research Fund
Association for International Cancer Research
Israel Cancer Association

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