Distinct roles for yeast Stn1 in telomere capping and telomerase inhibition

• Published in: The EMBO journal 2008-09, Vol.27 (17), p.2328-2339
• Main Authors: Puglisi, Andrea, Bianchi, Alessandro, Lemmens, Laure, Damay, Pascal, Shore, David
• Format: Article
• Language: English
• Subjects: Binding sites; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; CST complex; EMBO13; Genes, Fungal; Genetics; Molecular biology; Mutation; Protein Binding; Protein Structure, Tertiary; Proteins; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Stn1; telomerase; Telomerase - antagonists & inhibitors; Telomere - metabolism; telomere capping; telomere length regulation; Telomere-Binding Proteins - chemistry; Telomere-Binding Proteins - genetics; Telomere-Binding Proteins - metabolism; Yeast; Yeasts
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2008.158

The budding yeast Cdc13, Stn1 and Ten1 (CST) proteins are proposed to function as an RPA‐like complex at telomeres that protects (‘caps’) chromosome ends and regulates their elongation by telomerase. We show that Stn1 has a critical function in both processes through the deployment of two separable domains. The N terminus of Stn1 interacts with Ten1 and carries out its essential capping function. The C terminus of Stn1 binds both Cdc13 and Pol12, and we present genetic data indicating that the Stn1–Cdc13 interaction is required to limit continuous telomerase action. Stn1 telomere association, similar to that of Cdc13, peaks during S phase. Significantly, the magnitude of Stn1 telomere binding is independent of telomere TG tract length, suggesting that the negative effect of Stn1 on telomerase action might be regulated by a modification of CST activity or structure in cis at individual telomeres. Genetic analysis suggests that the Tel1 kinase exerts an effect in parallel with the Stn1 C terminus to counteract its inhibition of telomerase. These data provide new insights into the coordination of telomere capping and telomerase regulation.