Functional interaction between DNA-PKcs and telomerase in telomere length maintenance
| Autor: | Maria A. Blasco, Darren Gae, Susan M. Bailey, Sonia Franco, Guillermo E. Taccioli, Silvia Espejel, Antonella Sgura |
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| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Male
Telomerase Aging Cell division Somatic cell Telomere Capping Apoptosis DNA-Activated Protein Kinase Biology Protein Serine-Threonine Kinases General Biochemistry Genetics and Molecular Biology Chromosomes Mice Chromosome instability Catalytic Domain Neoplasms Protein Interaction Mapping Testis Animals Molecular Biology DNA-PKcs In Situ Hybridization Fluorescence Infertility Male Telomere-binding protein Chromosome Aberrations Mice Knockout General Immunology and Microbiology General Neuroscience Nuclear Proteins Articles Fibroblasts Telomere Molecular biology Spermatozoa DNA-Binding Proteins Mice Inbred C57BL enzymes and coenzymes (carbohydrates) Phenotype RNA biological phenomena cell phenomena and immunity Atrophy Cell Division Spleen |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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