The telomerase reverse transcriptase regulates chromatin state and DNA damage responses

Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8222-7. doi: 10.1073/pnas.0503095102. Epub 2005 May 31.


Constitutive expression of telomerase prevents senescence and crisis by maintaining telomere homeostasis. However, recent evidence suggests that telomerase is dynamically regulated in normal cells and also contributes to transformation independently of net telomere elongation. Here, we show that suppression of the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] expression abrogates the cellular response to DNA double strand breaks. Loss of hTERT does not alter short-term telomere integrity but instead affects the overall configuration of chromatin. Cells lacking hTERT exhibit increased radiosensitivity, diminished capacity for DNA repair, and fragmented chromosomes, demonstrating that loss of hTERT impairs the DNA damage response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Chromatin / chemistry
  • Chromatin / genetics*
  • Chromatin / metabolism*
  • DNA Damage*
  • DNA Repair
  • DNA-Binding Proteins
  • Fibroblasts
  • Humans
  • In Situ Hybridization, Fluorescence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Solubility
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / genetics
  • Telomere / metabolism


  • Chromatin
  • DNA-Binding Proteins
  • Telomerase