Processive and Distributive Extension of Human Telomeres by Telomerase under Homeostatic and Nonequilibrium Conditions

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 process...

Full description

Saved in:
Bibliographic Details
Published in:Molecular cell 2011-05, Vol.42 (3), p.297-307
Main Authors: Zhao, Yong, Abreu, Eladio, Kim, Jinyong, Stadler, Guido, Eskiocak, Ugur, Terns, Michael P., Terns, Rebecca M., Shay, Jerry W., Wright, Woodring E.
Format: Article
Language:English
Subjects:
acts
Blotting, Western
cell division
Cell Line, Tumor
Coiled Bodies - metabolism
G1 Phase
Gene Expression Regulation, Enzymologic - drug effects
HeLa Cells
Homeostasis
Humans
Models, Genetic
neoplasm cells
Oligonucleotides - pharmacology
Reverse Transcriptase Polymerase Chain Reaction
RNA
RNA Interference
S Phase
telomerase
Telomerase - antagonists & inhibitors
Telomerase - genetics
Telomerase - metabolism
Telomere - genetics
Telomere - metabolism
telomeres
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. [Display omitted] ► Telomerase displays two major distinct modes of action in human tumor cells ► A single molecule processively elongates each telomere at length homeostasis ► Multiple molecules successively elongate the ends when telomeres are elongating ► The processivity of telomerase is modulated in vivo
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2011.03.020