Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice

Silvia Espejel, Marta Martín, Peter Klatt, Juan Martín-Caballero, Juana M. Flores, María A. Blasco

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    Abstract

    Non-homologous end joining (NHEJ) is the principal repair mechanism used by mammalian cells to cope with double-strand breaks (DSBs) that continually occur in the genome. One of the key components of the mammalian NHEJ machinery is the DNA-PK complex, formed by the Ku86/70 heterodimer and the DNA-PK catalytic subunit (DNA-PKcs). Here, we report on the detailed life-long follow-up of DNA-PKcs-defective mice. Apart from defining a role of DNA-PKcs in telomere length maintenance in the context of the ageing organism, we observed that DNA-PKcs-defective mice had a shorter life span and showed an earlier onset of ageing-related pathologies than the corresponding wild-type littermates. in addition, DNA-PKcs ablation was associated with a markedly higher incidence of T lymphomas and infections. In conclusion, these data link the dual role of DNA-PKcs in DNA repair and telomere length maintenance to organismal ageing and cancer. © 2004 European Molecular Biology Organization.
    Original languageEnglish
    Pages (from-to)503-509
    JournalEMBO Reports
    Volume5
    Issue number5
    DOIs
    Publication statusPublished - 1 May 2004

    Keywords

    • Ageing
    • Cancer
    • DNA repair
    • DNA-PKcs
    • Telomeres

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    Espejel, S., Martín, M., Klatt, P., Martín-Caballero, J., Flores, J. M., & Blasco, M. A. (2004). Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice. EMBO Reports, 5(5), 503-509. https://doi.org/10.1038/sj.embor.7400127