• Open Access

Cytogenetic analysis of human cells reveals specific patterns of DNA damage in replicative and oncogene-induced senescence

Authors


Correspondence

Marco Crescenzi, Department of Cell Biology and Neurosciences, Italian National Institute of Health, Viale Regina Elena, 299, Roma 00161, Italy. Tel.: +39 064990 3163; fax: +39 064 990 2040; e-mail: marco.crescenzi@iss.it

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.

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