000184444 001__ 184444
000184444 005__ 20190416220715.0
000184444 0247_ $$2doi$$a10.1038/nature11269
000184444 022__ $$a0028-0836
000184444 02470 $$2ISI$$a000307761600043
000184444 037__ $$aARTICLE
000184444 245__ $$aThe human CST complex is a terminator of telomerase activity
000184444 260__ $$bNature Publishing Group$$c2012$$aLondon
000184444 269__ $$a2012
000184444 300__ $$a7
000184444 336__ $$aJournal Articles
000184444 520__ $$aThe lengths of human telomeres, which protect chromosome ends from degradation and end fusions(1,2), are crucial determinants of cell lifespan(3). During embryogenesis and in cancer, the telomerase enzyme counteracts telomeric DNA shortening. As shown in cancer cells, human telomerase binds the shelterin component TPP1 at telomeres(4,5) during the S phase of the cell cycle, and adds similar to 60 nucleotides in a single round of extension(6), after which telomerase is turned off by unknown mechanisms. Here we show that the human CST (CTC1, STN1 and TEN1) complex, previously implicated in telomere protection and DNA metabolism(7-11), inhibits telomerase activity through primer sequestration and physical interaction with the protection of telomeres 1 (POT1)-TPP1 telomerase processivity factor(12,13). CST competes with POT1-TPP1 for telomeric DNA, and CST-telomeric-DNA binding increases during late S/G2 phase only on telomerase action, coinciding with telomerase shut-off. Depletion of CST allows excessive telomerase activity, promoting telomere elongation. We propose that through binding of the telomerase-extended telomere, CST limits telomerase action at individual telomeres to approximately one binding and extension event per cell cycle. Our findings define the sequence of events that occur to first enable and then terminate telomerase-mediated telomere elongation.
000184444 700__ $$0243154$$g191071$$aChen, Liuh-Yow
000184444 700__ $$0243149$$g181958$$aRedon, Sophie
000184444 700__ $$aLingner, Joachim$$g168670$$0240570
000184444 773__ $$j488$$tNature$$k7412$$q540-4
000184444 8564_ $$uhttps://infoscience.epfl.ch/record/184444/files/nature11269.pdf$$zPublisher's version$$s1872824$$yPublisher's version
000184444 909C0 $$xU11159$$0252147$$pUPLIN
000184444 909CO $$ooai:infoscience.tind.io:184444$$qGLOBAL_SET$$pSV$$particle
000184444 917Z8 $$x168670
000184444 917Z8 $$x182396
000184444 937__ $$aEPFL-ARTICLE-184444
000184444 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000184444 980__ $$aARTICLE