Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase

Michel M. Ouellette, Martha Liao, Brittney Shea Herbert, Mari Johnson, Shawn E. Holt, Heidi S. Liss, Jerry W. Shay, Woodring E. Wright

Research output: Contribution to journalArticle

198 Scopus citations

Abstract

Human fibroblasts expressing the catalytic component of human telomerase (hTERT) have been followed for 250-400 population doublings. As expected, telomerase activity declined in long term culture of stable transfectants. Surprisingly, however, clones with average telomere lengths several kilobases shorter than those of senescent parental cells continued to proliferate. Although the longest telomeres shortened, the size of the shortest telomeres was maintained. Cells with subsenescent telomere lengths proliferated for an additional 20 doublings after inhibiting telomerase activity with a dominant- negative hTERT mutant. These results indicate that, under conditions of limiting telomerase activity, cis-acting signals may recruit telomerase to act on the shortest telomeres, argue against the hypothesis that the mortality stage 1 mechanism of cellular senescence is regulated by telomere positional effects (in which subtelomeric loci silenced by long telomeres are expressed when telomeres become short), and suggest that catalytically active telomerase is not required to provide a protein-capping role at the end of very short telomeres.

Original languageEnglish (US)
Pages (from-to)10072-10076
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number14
DOIs
StatePublished - Apr 7 2000

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ouellette, M. M., Liao, M., Herbert, B. S., Johnson, M., Holt, S. E., Liss, H. S., Shay, J. W., & Wright, W. E. (2000). Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase. Journal of Biological Chemistry, 275(14), 10072-10076. https://doi.org/10.1074/jbc.275.14.10072