Garg Mansi, Gurung Resham L, Mansoubi Sahar, Ahmed Jubed O, Davé Anoushka, Watts Felicity Z, Bianchi Alessandro
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK.
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK
EMBO Rep. 2014 Aug;15(8):871-7. doi: 10.15252/embr.201438919. Epub 2014 Jun 12.
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.
端粒酶介导的端粒悬突延长会被CST复合物（由CTC1（Cdc13）/Stn1/Ten1组成）合成互补链的过程所抵消。Cdc13的SUMO化作用增强了芽殖酵母Stn1与悬突结合蛋白Cdc13之间的相互作用。而人类和裂殖酵母的CST则与悬突结合蛋白TPP1/POT1相互作用。我们发现裂殖酵母中TPP1的直系同源物Tpz1会发生SUMO化。Tpz1的SUMO化作用限制了端粒的延长，并促进了Stn1/Ten1与端粒的结合，而且SUMO-Tpz1融合蛋白对Stn1的亲和力增强。我们的数据表明，SUMO通过刺激Tpz1介导的Stn1/Ten1作用来抑制端粒酶，这突出了SUMO化对CST功能调控在进化上的保守性。
