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.