000162188 001__ 162188
000162188 005__ 20190316235017.0
000162188 022__ $$a1098-5549
000162188 02470 $$2ISI$$a000277997900011
000162188 0247_ $$2doi$$a10.1128/MCB.00240-10
000162188 037__ $$aARTICLE
000162188 245__ $$aTIN2-tethered TPP1 recruits human telomerase to telomeres in vivo
000162188 269__ $$a2010
000162188 260__ $$bAmerican Society for Microbiology$$c2010
000162188 336__ $$aJournal Articles
000162188 500__ $$aCorresponding authors: J. Lingner & M. P. Terms Co-first authors: E. Abreu & E. Aritonovska
000162188 520__ $$aRecruitment to telomeres is a pivotal step in the function and regulation of human telomerase; however, the molecular basis for recruitment is not known. Here, we have directly investigated the process of telomerase recruitment via fluorescence in situ hybridization (FISH) and chromatin immunoprecipitation (ChIP). We find that depletion of two components of the shelterin complex that is found at telomeres--TPP1 and the protein that tethers TPP1 to the complex, TIN2--results in a loss of telomerase recruitment. On the other hand, we find that the majority of the observed telomerase association with telomeres does not require POT1, the shelterin protein that links TPP1 to the single-stranded region of the telomere. Deletion of the oligonucleotide/oligosaccharide binding fold (OB-fold) of TPP1 disrupts telomerase recruitment. In addition, while loss of TPP1 results in the appearance of DNA damage factors at telomeres, the DNA damage response per se does not account for the telomerase recruitment defect observed in the absence of TPP1. Our findings indicate that TIN2-anchored TPP1 plays a major role in the recruitment of telomerase to telomeres in human cells and that recruitment does not depend on POT1 or interaction of the shelterin complex with the single-stranded region of the telomere.
000162188 6531_ $$aDna-Damage Response
000162188 6531_ $$aEnd-Binding Protein
000162188 6531_ $$aHuman Cancer-Cells
000162188 6531_ $$aCajal Bodies
000162188 6531_ $$aDysfunctional Telomeres
000162188 6531_ $$aDyskeratosis-Congenita
000162188 6531_ $$aReverse-Transcriptase
000162188 6531_ $$aLength Homeostasis
000162188 6531_ $$aRna
000162188 6531_ $$aPot1
000162188 700__ $$aAbreu, Eladio
000162188 700__ $$0243148$$aAritonovska, Elena$$g176579
000162188 700__ $$aReichenbach, Patrick
000162188 700__ $$aCristofari, Gaël
000162188 700__ $$aCulp, Brad
000162188 700__ $$aTerns, Rebecca M.
000162188 700__ $$0240570$$aLingner, Joachim$$g168670
000162188 700__ $$aTerns, Michael P.
000162188 773__ $$j30$$k12$$q2971-82$$tMolecular and cellular biology
000162188 8564_ $$s3697052$$uhttps://infoscience.epfl.ch/record/162188/files/abreu%2Caritonovska0240-10.pdf$$yn/a$$zn/a
000162188 909C0 $$0252147$$pUPLIN$$xU11159
000162188 909CO $$ooai:infoscience.tind.io:162188$$pSV$$particle$$qGLOBAL_SET
000162188 917Z8 $$x168670
000162188 917Z8 $$x148230
000162188 937__ $$aEPFL-ARTICLE-162188
000162188 973__ $$aEPFL$$rNON-REVIEWED$$sPUBLISHED
000162188 980__ $$aARTICLE