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Molecular and Cellular Biology, April 2002, p. 2182-2193, Vol. 22, No. 7
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.7.2182-2193.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Maintenance of Double-Stranded Telomeric Repeats as the Critical Determinant for Cell Viability in Yeast Cells Lacking Ku

Serge Gravel,{dagger} and Raymund J. Wellinger*

Department of Microbiology, RNA Group/Groupe ARN, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada

Received 23 October 2001/ Returned for modification 18 December 2001/ Accepted 7 January 2002

The Saccharomyces cerevisiae Ku complex, while important for nonhomologous DNA end joining, is also necessary for maintaining wild-type telomere length and a normal chromosomal DNA end structure. Yeast cells lacking Ku can grow at 23°C but are unable to do so at elevated temperatures due to an activation of DNA damage checkpoints. To gain insights into the mechanisms affected by temperature in such strains, we isolated and characterized a new allele of the YKU70 gene, yku70-30ts. By several criteria, the Yku70-30p protein is functional at 23°C and nonfunctional at 37°C. The analyses of telomeric repeat maintenance as well as the terminal DNA end structure in strains harboring this allele alone or in strains with a combination of other mutations affecting telomere maintenance show that the altered DNA end structure in yeast cells lacking Ku is not generated in a telomerase-dependent fashion. Moreover, the single-stranded G-rich DNA on such telomeres is not detected by DNA damage checkpoints to arrest cell growth, provided that there are sufficient double-stranded telomeric repeats present. The results also demonstrate that mutations in genes negatively affecting G-strand synthesis (e.g., RIF1) or C-strand synthesis (e.g., the DNA polymerase {alpha} gene) allow for the maintenance of longer telomeric repeat tracts in cells lacking Ku. Finally, extending telomeric repeat tracts in such cells at least temporarily suppresses checkpoint activation and growth defects at higher temperatures. Thus, we hypothesize that an aspect of the coordinated synthesis of double-stranded telomeric repeats is sensitive to elevated temperatures.

* Corresponding author. Mailing address: Department of Microbiology, Faculty of Medicine, Université de Sherbrooke, 3001 12 Ave. N., Sherbrooke, Quebec J1H 5N4, Canada. Phone: (819) 564-5214. Fax: (819) 564-5392. E-mail: R.Wellin{at}courrier.usherb.ca.

{dagger} Present address: Wellcome/CRC Institute, Cambridge University, Cambridge CB2 1QR, United Kingdom.

Molecular and Cellular Biology, April 2002, p. 2182-2193, Vol. 22, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.7.2182-2193.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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