Identification of ATPases Pontin and Reptin as Telomerase Components Essential for Holoenzyme Assembly

Andrew S. Venteicher, Zhaojing Meng, Philip J. Mason, Timothy D. Veenstra, Steven E. Artandi

Research output: Contribution to journalArticlepeer-review

265 Scopus citations

Abstract

Telomerase is a multisubunit ribonucleoprotein (RNP) complex that adds telomere repeats to the ends of chromosomes. Three essential telomerase components have been identified thus far: the telomerase reverse transcriptase (TERT), the telomerase RNA component (TERC), and the TERC-binding protein dyskerin. Few other proteins are known to be required for human telomerase function, limiting our understanding of both telomerase regulation and mechanisms of telomerase action. Here, we identify the ATPases pontin and reptin as telomerase components through affinity purification of TERT from human cells. Pontin interacts directly with both TERT and dyskerin, and the amount of TERT bound to pontin and reptin peaks in S phase, evidence for cell-cycle-dependent regulation of TERT. Depletion of pontin and reptin markedly impairs telomerase RNP accumulation, indicating an essential role in telomerase assembly. These findings reveal an unanticipated requirement for additional enzymes in telomerase biogenesis and suggest alternative approaches for inhibiting telomerase in cancer.

Original languageEnglish (US)
Pages (from-to)945-957
Number of pages13
JournalCell
Volume132
Issue number6
DOIs
StatePublished - Mar 21 2008
Externally publishedYes

Bibliographical note

Funding Information:
We thank R. Kornberg, Y. Takagi, P. Jackson, G. Crabtree, M. Nachury, R. Verdun, J. Karlseder, T. Wang, G. Attardi, L. Attardi, J. Sage, A. Brunet, and K. McCann for helpful discussions and insights. We thank R. Dickins and S. Lowe for providing shRNA plasmids. A.S.V. was supported by Medical Scientist Training Program Grant GM07365. P.J.M. was supported by R01 CA106995. This project has been funded in part with federal funds from the NCI, NIH, under contract NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the United States Government. This work was supported by grants CA111691 and CA125453 from the NCI and by a grant from the American Federation of Aging Research/Pfizer to S.E.A.

Keywords

  • CELLBIO
  • PROTEINS

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