Tpz1 ^{TPP 1} SUMO ylation reveals evolutionary conservation of SUMO ‐dependent Stn1 telomere association

Abstract

Elongation of the telomeric overhang by telomerase is counteracted by synthesis of the complementary strand by the CST complex, CTC1(Cdc13)/Stn1/Ten1. Interaction of budding yeast Stn1 with overhang-binding Cdc13 is increased by Cdc13 SUMOylation. Human and fission yeast CST instead interact with overhang-binding TPP1/POT1. We show that the fission yeast TPP1 ortholog, Tpz1, is SUMOylated. Tpz1 SUMOylation restricts telomere elongation and promotes Stn1/Ten1 telomere association, and a SUMO-Tpz1 fusion protein has increased affinity for Stn1. Our data suggest that SUMO inhibits telomerase through stimulation of Stn1/Ten1 action by Tpz1, highlighting the evolutionary conservation of the regulation of CST function by SUMOylation.

SUMO-mediated regulation of DNA damage repair and responses

“…In the second study, limiting the sumoylation of the DNA end resection factors Sae2 (Sporulation in the Absence of Spo Eleven) and the Mre11-Rad50-Xrs2 (MRX) complex resulted in a stronger defect in processing DNA ends at DSBs than compromising that of either [52]. The ensemble effect also appears to occur at telomeres [37, 53–56]. For example, sumoylation of the telomerase regulators, namely Cdc13 and Tpz1 in budding and fission yeast, respectively, restrains telomerase function by facilitating the action of the telomerase inhibitor complex Stn1-Ten1 [37, 53, 54].…”

“…The ensemble effect also appears to occur at telomeres [37, 53–56]. For example, sumoylation of the telomerase regulators, namely Cdc13 and Tpz1 in budding and fission yeast, respectively, restrains telomerase function by facilitating the action of the telomerase inhibitor complex Stn1-Ten1 [37, 53, 54]. However, eliminating Cdc13 sumoylation causes less severe telomere defects than those arising from impaired global sumoylation in a SUMO E2 mutant [37].…”

“…The effects of sumoylation of fission yeast Tpz1 are much stronger than that of budding yeast Cdc13 [37, 53, 54], suggesting an organism-based difference and providing an example for the star effect model. Another example for this model is that of the FANCI and FANCD2 proteins whose sumoylation appears to be critical for their function in DNA repair [32].…”

Dynamic Interactions of Arabidopsis TEN1: Stabilizing Telomeres in Response to Heat Stress

“…Telomere length homeostasis is achieved by a highly orchestrated, but poorly understood, series of conformational changes that sequentially convert the G-overhang into telomerase-extendable and nonextendable states (Blackburn, 2001;Teixeira et al, 2004). This binary switch is controlled by longrange protein interactions (Loayza and De Lange, 2003;Marcand et al, 1997), dynamic shifts among core components of telomere complexes (Jun et al, 2013), and posttranslational modification (Garg et al, 2014;Liu et al, 2014;Miyagawa et al, 2014;Zhang et al, 2013).…”

Ubiquitination and SUMOylation in Telomere Maintenance and Dysfunction

“…In Schizosaccharomyces pombe (fission yeast) SUMOylation of Tpz1, the homolog of TPP1, has been connected to negative regulation of telomere elongation (Hang et al, 2011; Garg et al, 2014; Miyagawa et al, 2014). SUMOylation of Tpz1 decreases telomerase binding to telomeres.…”