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Molecular and Cellular Biology, December 2003, p. 9162-9177, Vol. 23, No. 24
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.24.9162-9177.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Mitotic Cyclins Regulate Telomeric Recombination in Telomerase-Deficient Yeast Cells

Nathalie Grandin and Michel Charbonneau*

IFR128 BioSciences Gerland, UMR CNRS/ENS no. 5665, Ecole Normale Supérieure de Lyon, 69364 Lyon, France

Received 25 June 2003/ Returned for modification 11 August 2003/ Accepted 16 September 2003

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 TG1-3 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.

* Corresponding author. Mailing address: IFR128 BioSciences Gerland, Ecole Normale Supérieure de Lyon, UMR CNRS 5665, 46, allée d'Italie, 69364 Lyon, France. Phone: (33) 472 72 81 70. Fax: (33) 472 72 80 80. E-mail: Michel.Charbonneau{at}ens-lyon.fr.

Molecular and Cellular Biology, December 2003, p. 9162-9177, Vol. 23, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.24.9162-9177.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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