Suppression of hPOT1 in diploid human cells results in an hTERT-dependent alteration of telomere length dynamics

Richard Possemato, Jamie C. Timmons, Erica L. Bauerlein, Naoya Wada, Amy Baldwin, Kenkichi Masutomi, William C. Hahn

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

POT1 is a 3′ telomeric single-stranded overhang binding protein that has been implicated in chromosome end protection,the regulation of telomerase function,and defining the 5′ chromosome terminus. In human cancer cells that exhibit constitutive hTERT activity, hPOT1 exerts control over telomere length. Primary human fibroblasts express low levels of catalytically active hTERT in an S-phase-restricted manner that fails to counteract telomere attrition with cell division. Here, we show that diploid human fibroblasts in which hPOT1 expression has been suppressed harbor telomeres that are longer than control cells. This difference in telomere length delays the onset of replicative senescence and is dependent on S-phase-restricted hTERT expression. These findings are consistent with the view that hPOT1 promotes a nonextendable telomere state resistant to extension by S-phase-restricted telomerase. Manipulating this function of hPOT1 may thus hasten the cytotoxic effects of telomerase inhibition.

Original languageEnglish (US)
Pages (from-to)1582-1593
Number of pages12
JournalMolecular Cancer Research
Volume6
Issue number10
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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