Journal
MOLECULAR CELL
Volume 42, Issue 3, Pages 297-307Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2011.03.020
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Funding
- National Institute on Aging [AG01228]
- National Cancer Institute [CA104676]
- American Federation for Aging Research
- National Institutes of Health [F31GM087949]
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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 similar to 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.
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