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.
| Original language | English |
|---|---|
| Pages (from-to) | 312-315 |
| Number of pages | 4 |
| Journal | Aging Cell |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2013 |
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Keywords
- Cell cycle inhibitors
- Cytogenetic analysis
- DNA damage
- Oncogene-induced senescence
- Replicative senescence
- Telomerase
ASJC Scopus subject areas
- Cell Biology
- Ageing
Cite this
Cytogenetic analysis of human cells reveals specific patterns of DNA damage in replicative and oncogene-induced senescence. / Falcone, Germana; Mazzola, Alessia; Michelini, Flavia; Bossi, Gianluca; Censi, Federica; Biferi, Maria G.; Minghetti, Luisa; Floridia, Giovanna; Federico, Maurizio; Musio, Antonio; Crescenzi, Marco.
In: Aging Cell, Vol. 12, No. 2, 2013, p. 312-315.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytogenetic analysis of human cells reveals specific patterns of DNA damage in replicative and oncogene-induced senescence
AU - Falcone, Germana
AU - Mazzola, Alessia
AU - Michelini, Flavia
AU - Bossi, Gianluca
AU - Censi, Federica
AU - Biferi, Maria G.
AU - Minghetti, Luisa
AU - Floridia, Giovanna
AU - Federico, Maurizio
AU - Musio, Antonio
AU - Crescenzi, Marco
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Cell cycle inhibitors
KW - Cytogenetic analysis
KW - DNA damage
KW - Oncogene-induced senescence
KW - Replicative senescence
KW - Telomerase
UR - http://www.scopus.com/inward/record.url?scp=84878950563&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878950563&partnerID=8YFLogxK
U2 - 10.1111/acel.12034
DO - 10.1111/acel.12034
M3 - Article
C2 - 23167636
AN - SCOPUS:84878950563
VL - 12
SP - 312
EP - 315
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 2
ER -