Functional interaction between DNA-PKcs and telomerase in telomere length maintenance

Silvia Espejel, Sonia Franco, Antonella Sgura, Darren Gae, Susan M. Bailey, Guillermo E. Taccioli, María A. Blasco

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


DNA-PKcs is the catalytic subunit of the DNA-dependent protein kinase (DNA-PK) complex that functions in the non-homologous end-joining of double-strand breaks, and it has been shown previously to have a role in telomere capping. In particular, DNA-PKcs deficiency leads to chromosome fusions involving telomeres produced by leading-strand synthesis. Here, by generating mice doubly deficient in DNA-PKcs and telomerase (Terc-/-/DNA-PKcs-/-), we demonstrate that DNA-PKcs also has a fundamental role in telomere length maintenance. In particular, Terc-/-/DNA-PKcs-/- mice displayed an accelerated rate of telomere shortening when compared with Terc-/- controls, suggesting a functional interaction between both activities in maintaining telomere length. In addition, we also provide direct demonstration that DNA-PKcs is essential for both end-to-end fusions and apoptosis triggered by critically short telomeres. Our data predict that, in telomerase-deficient cells, i.e. human somatic cells, DNA-PKcs abrogation may lead to a faster rate of telomere degradation and cell cycle arrest in the absence of increased apoptosis and/or fusion of telomere-exhausted chromosomes. These results suggest a critical role of DNA-PKcs in both cancer and aging.

Original languageEnglish (US)
Pages (from-to)6275-6287
Number of pages13
JournalEMBO Journal
Issue number22
StatePublished - Nov 15 2002
Externally publishedYes


  • Apoptosis
  • Chromosome fusions
  • DNA-PKcs
  • Telomerase
  • Telomere length

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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