Distinct roles for yeast Stn1 in telomere capping and telomerase inhibition

Abstract

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 Tell 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.

Human Stn1 protects telomere integrity by promoting efficient lagging-strand synthesis at telomeres and mediating C-strand fill-in

“…The budding yeast CST complex restricts excessive C-strand resection from telomere ends, interacts with polα to mediate C-strand fill-in, and regulates telomerase activity [14][15][16][17][18][19][20][21][22]. While hStn1 may retain the functions in telomerespecific C-strand fill-in and regulating telomerase, it may have no role in restraining excessive end resection at leading daughter telomeres ( Figure 5D).…”

“…In yeasts and plants, homologs of CST appear to ensure telomere stability by capping chromosome ends [3,[11][12][13][14][15][16][17][18][19][20][21][22]. In vertebrates, the capping function is achieved by shelterin proteins.…”

“…In budding yeast, the Cdc13/Stn1/Ten1 complex associates exclusively with the G-overhang and plays important roles in restricting excessive C-strand resection from telomere ends, mediating C-strand fill-in, and regulating telomerase activity [14][15][16][17][18][19][20][21][22]. In fission yeast, orthologs of Stn1 and Ten1 have been identified and they are essential for cell growth.…”

“…In yeasts and plants, homologs of CST are critical for ensuring telomere stability [3,[11][12][13][14][15][16][17][18][19][20][21][22]. In budding yeast, the Cdc13/Stn1/Ten1 complex associates exclusively with the G-overhang and plays important roles in restricting excessive C-strand resection from telomere ends, mediating C-strand fill-in, and regulating telomerase activity [14][15][16][17][18][19][20][21][22].…”

CDK1 differentially regulates G-overhang generation at leading- and lagging-strand telomeres in telomerase-negative cells in G2phase

“…In yeast, end resection is limited by the telomere protection protein complex Cdc13/Stn1/Ten1. [44][45][46] In mammalian cells, Pot1b appears to play this role. 14,47,48 However, depletion of human Pot1 leads to G-overhang shortening, 6,8 contradicting the expectation from protecting C-strand from degradation.…”