Mitotic cyclins regulate telomeric recombination in telomerase-deficient yeast cells.
Telomerase-deficient mutants of Saccharomyces cerevisiae can survive death by senescence by using one of two homologous recombination pathways. The Rad51 pathway amplifies the subtelomeric Y' sequences, while the Rad50 pathway amplifies the telomeric TG(1-3) repeats. Here we show that telomerase-negative cells require Clb2 (the major B-type cyclin in this organism), in association with Cdc28 (Cdk1), to generate postsenescence survivors at a normal rate. The Rad50 pathway was more sensitive to the absence of Clb2 than the Rad51 pathway. We also report that telomerase RAD50 RAD51 triple mutants still generated postsenescence survivors. This novel Rad50- and Rad51-independent pathway of telomeric recombination also appeared to be controlled by Clb2. In telomerase-positive cells, a synthetic growth defect between mutations in CLB2 and RAD50 or in its partners in the conserved MRX complex, MRE11 and XRS2, was observed. This genetic interaction was independent of Mre11 nuclease activity but was dependent on a DNA repair function. The present data reveal an unexpected role of Cdc28/Clb2 in telomeric recombination during telomerase-independent maintenance of telomeres. They also uncover a functional interaction between Cdc28/Clb2 and MRX during the control of the mitotic cell cycle.
Grandin
Nathalie
N
IFR128 BioSciences Gerland, UMR CNRS/ENS no. 5665, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon, France.
Charbonneau
Michel
M
D016203:CDC2 Protein Kinase / Q000378:metabolism; D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004720:Endonucleases; D005090:Exodeoxyribonucleases / Q000378:metabolism; D008938:Mitosis; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*
C093749:CLB2 protein, S cerevisiae; D019926:Cyclin B; D016213:Cyclins; D004268:DNA-Binding Proteins; C086930:RAD50 protein, S cerevisiae; C400213:RAD59 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae; D019098:Telomerase; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; C411624:MUS81 protein, S cerevisiae