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

SummarySpecific 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.

Graphical AbstractFigure optionsDownload high-quality image (124 K)Download as PowerPoint slideHighlights
► 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