Hsp90 levels affect telomere length in yeast

Cdc13 is a Saccharomyces cerevisiae protein that binds to telomeric single-stranded DNA and regulates telomerase activity. Stn1 has been shown by two-hybrid analysis to form a physical complex with Cdc13. Temperature-sensitive mutations in CDC13 and STN1 , which are both essential genes, activate a DNA damage-dependent checkpoint which is the cause of the arrest seen in the mutant strains. The stn1 - 13 mutation induces dramatic telomere elongation which is telomerase dependent, as shown here. Additional mutants for STN1 , which show a tighter arrest phenotype than stn1 - 13 , were generated in order to perform genetic screens aiming at uncovering new regulators of telomerase. HSC82 , which encodes a conserved molecular chaperone of the Hsp90 family, was thus isolated as a high-dosage suppressor of a temperature-sensitive mutation in STN1 . Overexpression of HSC82 also partially suppressed the growth defect of cdc13 - 1 cells. Overexpression of HSC82 was found to correct the telomeric defect associated with stn1 mutations. Shortening of telomeres was also observed in wild-type cells upon overexpression of HSC82 , or of its temperature-inducible homologue, HSP82 . These results identify Hsc82/Hsp82 as potential regulators of telomerase in yeast cells.