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| Curr. Genet. Feb (2007); 51(2):123-40 | |
| A role for the yeast cell cycle-splicing factor Cdc40 in the G1-S transition- | |
| Kaplan Y, Kupiec M | |
| Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, 69978, Israel- | |
| 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 G-1--S transition, progress slowly through S-phase and arrest at a restrictive temperature in the G-2- 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 G-1--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 G-1--S -START- is further supported by the enhanced temperature sensitivity and G-1--S transition phenotype of a cdc40 strain lacking the G-1- 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- | |
| [PUBMED: 17171376] |   |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |