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.
© 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cells, Cultured
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Cellular Senescence / genetics*
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p21 / antagonists & inhibitors
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Cyclin-Dependent Kinase Inhibitor p21 / genetics*
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Cytogenetic Analysis
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DNA Damage*
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Genetic Vectors
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Humans
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Lentivirus / genetics
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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Oncogenes*
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RNA, Small Interfering / genetics
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Telomerase / antagonists & inhibitors
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Telomerase / genetics*
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Telomerase / metabolism
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Telomere / genetics
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Telomere / metabolism
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Telomere / pathology
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Transduction, Genetic
Substances
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CDKN2A protein, human
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p21
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Neoplasm Proteins
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RNA, Small Interfering
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TERT protein, human
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Telomerase