Open AccessCytogenetic analysis of human cells reveals specific patterns of DNA damage in replicative and oncogene‐induced senescence
Author(s) -
Falcone Germana,
Mazzola Alessia,
Michelini Flavia,
Bossi Gianluca,
Censi Federica,
Biferi Maria G.,
Minghetti Luisa,
Floridia Giovanna,
Federico Maurizio,
Musio Antonio,
Crescenzi Marco
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12034
Subject(s) - dna damage , biology , senescence , telomere , telomerase , oncogene , dna , microbiology and biotechnology , genetics , telomerase reverse transcriptase , cancer research , gene , cell cycle
Summary 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.