Hsp90 levels affect telomere length in yeast.
Cdc13 is a Saccharomyces cerevisiae protein that binds to telomeric single-stranded DNA and regulates telomerase activity. Stnl 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.
Grandin
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N
UMR CNRS 5665, Ecole Normale Supérieure, Lyon, France.
Charbonneau
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M
D015152:Blotting, Northern; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D018816:Genes, cdc; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006358:Hot Temperature; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; D019926:Cyclin B; D004277:DNA, Single-Stranded; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; C428109:Stn1 protein, S cerevisiae; D034501:Telomere-Binding Proteins; D019098:Telomerase