title: Cytogenetic analysis of human cells reveals specific patterns of DNA damage in replicative and oncogene-induced senescence.
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.
authors.affiliation: Department of Cell Biology and Neurosciences, National Institute of Health, Rome, Italy.
authors.forename: Germana
authors.initials: G
authors.lastname: Falcone
authors.forename: Alessia
authors.initials: A
authors.lastname: Mazzola
authors.forename: Flavia
authors.initials: F
authors.lastname: Michelini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bossi
authors.forename: Federica
authors.initials: F
authors.lastname: Censi
authors.forename: Maria G
authors.initials: MG
authors.lastname: Biferi
authors.forename: Luisa
authors.initials: L
authors.lastname: Minghetti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Floridia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Federico
authors.forename: Antonio
authors.initials: A
authors.lastname: Musio
authors.forename: Marco
authors.initials: M
authors.lastname: Crescenzi
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020732:Cytogenetic Analysis; D004249:DNA Damage; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D034741:RNA, Small Interfering / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C509186:TERT protein, human; D019098:Telomerase