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 journalArticle

Abstract

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
JournalThe EMBO journal
Volume21
Issue number22
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

Fingerprint

Telomere Homeostasis
Telomerase
Telomere
DNA
Fusion reactions
Chromosomes
DNA-Activated Protein Kinase
Catalytic DNA
Apoptosis
Telomere Shortening
Cell Cycle Checkpoints
Joining
Catalytic Domain
Demonstrations
Aging of materials
Cells

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Espejel, S., Franco, S., Sgura, A., Gae, D., Bailey, S. M., Taccioli, G. E., & Blasco, M. A. (2002). Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. The EMBO journal, 21(22), 6275-6287. https://doi.org/10.1093/emboj/cdf593

Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. / Espejel, Silvia; Franco, Sonia; Sgura, Antonella; Gae, Darren; Bailey, Susan M.; Taccioli, Guillermo E.; Blasco, María A.

In: The EMBO journal, Vol. 21, No. 22, 15.11.2002, p. 6275-6287.

Research output: Contribution to journalArticle

Espejel, S, Franco, S, Sgura, A, Gae, D, Bailey, SM, Taccioli, GE & Blasco, MA 2002, 'Functional interaction between DNA-PKcs and telomerase in telomere length maintenance', The EMBO journal, vol. 21, no. 22, pp. 6275-6287. https://doi.org/10.1093/emboj/cdf593
Espejel S, Franco S, Sgura A, Gae D, Bailey SM, Taccioli GE et al. Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. The EMBO journal. 2002 Nov 15;21(22):6275-6287. https://doi.org/10.1093/emboj/cdf593
Espejel, Silvia ; Franco, Sonia ; Sgura, Antonella ; Gae, Darren ; Bailey, Susan M. ; Taccioli, Guillermo E. ; Blasco, María A. / Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. In: The EMBO journal. 2002 ; Vol. 21, No. 22. pp. 6275-6287.
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