Massive telomere loss is an early event of DNA damage-induced apoptosis

J Biol Chem. 2003 Jan 10;278(2):836-42. doi: 10.1074/jbc.M206818200. Epub 2002 Oct 29.

Abstract

Chromosomal stability and cell viability require a proficient telomeric end-capping function. In particular, telomere dysfunction because of either critical telomere shortening or because of mutation of telomere-binding proteins results in increased apoptosis and/or cell arrest. Here, we show that, in turn, DNA damage-induced apoptosis results in a dramatic telomere loss. In particular, using flow cytometry for simultaneous detection of telomere length and apoptosis, we show that cells undergoing apoptosis upon DNA damage also exhibit a rapid and dramatic loss of telomeric sequences. This telomere loss occurs at early stages of apoptosis, because it does not require caspase-3 activation, and it is induced by loss of the mitochondrial membrane potential (Deltapsi(m)) and production of reactive oxygen species. These observations suggest a direct effect of mitochondrial dysfunction on telomeres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Camptothecin / pharmacology
  • Caspase 3
  • Caspases / physiology
  • DNA Damage*
  • Enzyme Activation
  • Humans
  • Poly(ADP-ribose) Polymerases / physiology
  • Reactive Oxygen Species
  • Telomerase / metabolism
  • Telomere*
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • Poly(ADP-ribose) Polymerases
  • Telomerase
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Camptothecin