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Shorter telomeres, accelerated ageing and increased lymphoma in DNA‐PKcs‐deficient mice
Author(s) -
Espejel Silvia,
Martín Marta,
Klatt Peter,
MartínCaballero Juan,
Flores Juana M,
Blasco María A
Publication year - 2004
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400127
Subject(s) - telomere , dna pkcs , ku80 , ageing , biology , context (archaeology) , dna , dna repair , dna damage , non homologous end joining , microbiology and biotechnology , cancer research , genetics , gene , transcription factor , dna binding protein , paleontology
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.