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EMBO reports 5, 5, 503–509 (2004)
doi:10.1038/sj.embor.7400127
Published online: 23 April 2004
Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice
Silvia Espejel1, Marta Martín2, Peter Klatt1, Juan Martín-Caballero1, Juana M Flores3 & María A Blasco1
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1 Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029, Madrid, Spain
2 Department of Cell Biology, Physiology and Immunology, and Institute of Biotechnology and Biomedicine, Universitat Autonoma de Barcelona, Barcelona 08193, Spain
3 Animal Surgery and Medicine Department, Facultad de Veterinaria, Universidad Complutense de Madrid, E-28040, Madrid, Spain
To whom correspondence should be addressed
María A Blasco Tel: +34 917328031; Fax: +34 917328028; E-mail: mblasco@cnio.es
Received 2 December 2003; Accepted 18 February 2004; Published online 23 April 2004.
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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.
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