Cytogenetic analysis of human cells reveals specific patterns of DNA damage in replicative and oncogene‐induced senescence |
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| Authors: | Germana Falcone Alessia Mazzola Flavia Michelini Gianluca Bossi Federica Censi Maria G. Biferi Luisa Minghetti Giovanna Floridia Maurizio Federico Antonio Musio Marco Crescenzi |
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| Affiliation: | 1. Department of Cell Biology and Neurosciences, National Institute of Health, , Rome, Italy;2. Institute of Cell Biology and Neurobiology, National Research Council, , Monterotondo (Rome), Italy;3. Department of Molecular Oncology, Regina Elena Cancer Institute, , Rome, Italy;4. National Centre for Rare Diseases, National Institute of Health, , Rome, Italy;5. National AIDS Centre, National Institute of Health, , Rome, Italy;6. Institute of Genetic and Biomedical Research, National Research Council, , Pisa, Italy;7. Istituto Toscano Tumori, , Florence, Italy |
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| Abstract: | Senescence is thought to be triggered by DNA damage, usually indirectly assessed as activation of the DNA damage response (DDR), but direct surveys of genetic damage are lacking. Here, we mitotically reactivate senescent human fibroblasts to evaluate their cytogenetic damage. We show that replicative senescence is generally characterized by telomeric fusions. However, both telomeric and extratelomeric aberrations are prevented by hTERT, indicating that even non‐telomeric damage descends from the lack of telomerase. Compared with replicative senescent cells, oncogene‐induced senescent fibroblasts display significantly higher levels of DNA damage, depicting how oncogene activation can catalyze the generation of further, potentially tumorigenic, genetic damage. |
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| Keywords: | cell cycle inhibitors cytogenetic analysis DNA damage oncogene‐induced senescence replicative senescence telomerase |
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