title: Mechanism of heat stress-induced cellular senescence elucidates the exclusive vulnerability of early S-phase cells to mild genotoxic stress.
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.
authors.affiliation: Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
authors.forename: Artem K
authors.initials: AK
authors.lastname: Velichko
authors.affiliation: Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia Department of Molecular Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Petrova
authors.affiliation: Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia Department of Molecular Biology, Lomonosov Moscow State University, 119991 Moscow, Russia LIA 1066 French-Russian Joint Cancer Research Laboratory, 94805 Villejuif, France sergey.v.razin@usa.net.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Razin
authors.affiliation: Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia LIA 1066 French-Russian Joint Cancer Research Laboratory, 94805 Villejuif, France omar.kantidze@genebiology.ru.
authors.forename: Omar L
authors.initials: OL
authors.lastname: Kantidze
mesh_terms: D002166:Camptothecin / Q000494:pharmacology; D059447:Cell Cycle Checkpoints; D002478:Cells, Cultured; D016922:Cellular Senescence; D053904:DNA Breaks, Single-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D016196:S Phase / Q000235:genetics; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics*; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology
chemical_list: D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin