Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres

Silvia Espejel, Sonia Franco, Sandra Rodríguez-Perales, Simon D. Bouffler, Juan C. Cigudosa, María A. Blasco

Research output: Contribution to journalArticle

Abstract

Here we analyze the functional interaction between Ku86 and telomerase at the mammalian telomere by studying mice deficient for both proteins. We show that absence of Ku86 prevents the end-to-end chromosomal fusions that result from critical telomere shortening in telomerase-deficient mice. In addition, Ku86 deficiency rescues the male early germ cell apoptosis triggered by short telomeres in these mice. Together, these findings define a role for Ku86 in mediating chromosomal instability and apoptosis triggered by short telomeres. In addition, we show here that Ku86 deficiency results in telomerase-dependent telomere elongation and in the fusion of random pairs of chromosomes in telomerase-proficient cells, suggesting a model in which Ku86 keeps normal-length telomeres less accessible to telomerase-mediated telomere lengthening and to DNA repair activities.

Original languageEnglish (US)
Pages (from-to)2207-2219
Number of pages13
JournalThe EMBO journal
Volume21
Issue number9
DOIs
StatePublished - May 1 2002

Fingerprint

Telomerase
Telomere
Fusion reactions
Apoptosis
Telomere Homeostasis
Telomere Shortening
Chromosomal Instability
Chromosomes
Germ Cells
DNA Repair
Elongation
Repair
Cells
DNA
Proteins

Keywords

  • Apoptosis
  • Ku86
  • Telomerase
  • Telomere dysfunction

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Espejel, S., Franco, S., Rodríguez-Perales, S., Bouffler, S. D., Cigudosa, J. C., & Blasco, M. A. (2002). Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. The EMBO journal, 21(9), 2207-2219. https://doi.org/10.1093/emboj/21.9.2207

Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. / Espejel, Silvia; Franco, Sonia; Rodríguez-Perales, Sandra; Bouffler, Simon D.; Cigudosa, Juan C.; Blasco, María A.

In: The EMBO journal, Vol. 21, No. 9, 01.05.2002, p. 2207-2219.

Research output: Contribution to journalArticle

Espejel, S, Franco, S, Rodríguez-Perales, S, Bouffler, SD, Cigudosa, JC & Blasco, MA 2002, 'Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres', The EMBO journal, vol. 21, no. 9, pp. 2207-2219. https://doi.org/10.1093/emboj/21.9.2207
Espejel S, Franco S, Rodríguez-Perales S, Bouffler SD, Cigudosa JC, Blasco MA. Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. The EMBO journal. 2002 May 1;21(9):2207-2219. https://doi.org/10.1093/emboj/21.9.2207
Espejel, Silvia ; Franco, Sonia ; Rodríguez-Perales, Sandra ; Bouffler, Simon D. ; Cigudosa, Juan C. ; Blasco, María A. / Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. In: The EMBO journal. 2002 ; Vol. 21, No. 9. pp. 2207-2219.
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