Current Genetics

, Volume 51, Issue 2, pp 123–140 | Cite as

A role for the yeast cell cycle/splicing factor Cdc40 in the G1/S transition

Research Article

Abstract

The CDC40 (PRP17) gene of S. cerevisiae encodes a splicing factor required for multiple events in the mitotic and meiotic cell cycles, linking splicing with cell cycle control. cdc40 mutants exhibit a delayed G1/S transition, progress slowly through S-phase and arrest at a restrictive temperature in the G2 phase. In addition, they are hypersensitive to genotoxic agents such as methylmethane sulfonate (MMS) and Hydroxyurea (HU). CDC40 has been suggested to control cell cycle through splicing of intron-containing pre-mRNAs that encode proteins important for cell cycle progression. We screened a cDNA overexpression library and isolated cDNAs that specifically suppress the HU/MMS-sensitivity of cdc40 mutants. Most of these cDNAs surprisingly encode chaperones, translation initiation factors and glycolytic enzymes, and none of them is encoded by an intron-containing gene. Interestingly, the cDNAs suppress the G1/S transition delay of cdc40 cells, which is exacerbated by HU, suggesting that cdc40 mutants are HU/MMS-sensitive due to their S-phase entry defect. A role of Cdc40p in passage through G1/S (START) is further supported by the enhanced temperature sensitivity and G1/S transition phenotype of a cdc40 strain lacking the G1 cyclin, Cln2p. We provide evidence that the mechanism of suppression by the isolated cDNAs does not (at least solely) involve up-regulation of the known positive START regulators CLN2, CLN3, DCR2 and GID8, or of the large and small essential ribonucleotide reductase (RNR) subunits, RNR1 and RNR2. Finally, we discuss possible mechanisms of suppression by the cDNAs that imply cell cycle regulation by apparently unrelated processes, such as splicing, translation initiation and glycolysis.

Keywords

Cell cycle Hydroxyurea Methylmethane sulfonate Splicing Saccharomyces cerevisiae 

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Molecular Microbiology and BiotechnologyTel Aviv UniversityRamat AvivIsrael

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