Pseudo-DNA damage response in senescent cells.
Cellular senescence is currently viewed as a response to DNA damage. In this report, we showed that non-damaging agents such as sodium butyrate-induced p21 and ectopic expression of either p21 or p16 cause cellular senescence without detectable DNA breaks. Nevertheless, senescent cells displayed components of DNA damage response (DDR) such as gammaH2AX foci and uniform nuclear staining for p-ATM. Importantly, there was no accumulation of 53BP1 in gammaH2AX foci of senescent cells. Consistently, comet assay failed to detect DNA damage. Rapamycin, an inhibitor of mTO R, which was shown to suppress cellular senescence, decreased gammaH2AX foci formation. Thus, cellular senescence leads to activation of atypical DDR without detectable DNA damage. Pseudo-DDR may be a marker of general over-activation of senescent cells.
Pospelova
Tatyana V
TV
Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia. tvpgroup@mail.ru
Demidenko
Zoya N
ZN
Bukreeva
Elena I
EI
Pospelov
Valery A
VA
Gudkov
Andrei V
AV
Blagosklonny
Mikhail V
MV
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics*; D006657:Histones / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology; D013312:Stress, Physiological / Q000235:genetics; D058570:TOR Serine-Threonine Kinases
D015415:Biomarkers; C493956:CDKN1A protein, human; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D004247:DNA; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus