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Nucleic Acids Research, 2002, Vol. 30, No. 20 4361-4370
© 2002 Oxford University Press

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

Orna Dahan and Martin Kupiec*

Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel

*To whom correspondence should be addressed. Tel: +972 3 640 9031; Fax: +972 3 640 9407; Email: martin{at}post.tau.ac.il

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 isy1{Delta} syf2{Delta} 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 isy1{Delta} syf2{Delta} 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.


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