Mechanism of heat stress-induced cellular senescence elucidates the exclusive vulnerability of early S-phase cells to mild genotoxic stress |
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| Authors: | Artem K. Velichko Nadezhda V. Petrova Sergey V. Razin Omar L. Kantidze |
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| Affiliation: | 1.Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia;2.Department of Molecular Biology, Lomonosov Moscow State University, 119991 Moscow, Russia;3.LIA 1066 French-Russian Joint Cancer Research Laboratory, 94805 Villejuif, France |
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| Abstract: | Heat stress is one of the best-studied cellular stress factors; however, little is known about its delayed effects. Here, we demonstrate that heat stress induces p21-dependent cellular senescence-like cell cycle arrest. Notably, only early S-phase cells undergo such an arrest in response to heat stress. The encounter of DNA replication forks with topoisomerase I-generated single-stranded DNA breaks resulted in the generation of persistent double-stranded DNA breaks was found to be a primary cause of heat stress-induced cellular senescence in these cells. This investigation of heat stress-induced cellular senescence elucidates the mechanisms underlying the exclusive sensitivity of early S-phase cells to ultra-low doses of agents that induce single-stranded DNA breaks. |
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