title: Processive and distributive extension of human telomeres by telomerase under homeostatic and nonequilibrium conditions.
abstract: Specific information about how telomerase acts in vivo is necessary for understanding telomere dynamics in human tumor cells. Our results imply that, under homeostatic telomere length-maintenance conditions, only one molecule of telomerase acts at each telomere during every cell division and processively adds ∼60 nt to each end. In contrast, multiple molecules of telomerase act at each telomere when telomeres are elongating (nonequilibrium conditions). Telomerase extension is less processive during the first few weeks following the reversal of long-term treatment with the telomerase inhibitor Imetelstat (GRN163L), a time when Cajal bodies fail to deliver telomerase RNA to telomeres. This result implies that processing of telomerase by Cajal bodies may affect its processivity. Overexpressed telomerase is also less processive than the endogenously expressed telomerase. These findings reveal two major distinct extension modes adopted by telomerase in vivo.
authors.affiliation: Department of Cell Biology, University of Texas, Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Eladio
authors.initials: E
authors.lastname: Abreu
authors.forename: Jinyong
authors.initials: J
authors.lastname: Kim
authors.forename: Guido
authors.initials: G
authors.lastname: Stadler
authors.forename: Ugur
authors.initials: U
authors.lastname: Eskiocak
authors.forename: Michael P
authors.initials: MP
authors.lastname: Terns
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Terns
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D020541:Coiled Bodies / Q000378:metabolism; D016193:G1 Phase; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D008957:Models, Genetic; D009841:Oligonucleotides / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*
chemical_list: C505952:GRN163L peptide; D009841:Oligonucleotides; C509186:TERT protein, human; D019098:Telomerase