title: Early S-phase cell hypersensitivity to heat stress.
abstract: Heat stress is one of the best-studied exogenous stress factors; however little is known about its delayed effects. Recently, we have shown that heat stress induces cellular senescence-like G2 arrest exclusively in early S-phase cells. The mechanism of this arrest includes the generation of heat stress-induced single-stranded DNA breaks, the collision of replication forks with these breaks and the formation of difficult-to-repair double-stranded DNA breaks. However, the early S phase-specific effects of heat stress are not limited to the induction of single-stranded DNA breaks. Here, we report that HS induces partial DNA re-replication and centrosome amplification. We suggest that HS-induced alterations in the expression levels of the genes encoding the replication licensing factors are the primary source of such perturbations. Notably, these processes do not contribute to acquisition of a senescence-like phenotype, although they do elicit postponed effects. Specifically, we found that the HeLa cells can escape from the heat stress-induced cellular senescence-like G2 arrest, and the mitosis they enter is multipolar due to the amplified centrosomes.
authors.affiliation: a Institute of Gene Biology, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Petrova
authors.affiliation: a Institute of Gene Biology, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Artem K
authors.initials: AK
authors.lastname: Velichko
authors.affiliation: a Institute of Gene Biology, Russian Academy of Sciences , Moscow , Russia.|b Department of Molecular Biology , Lomonosov Moscow State University , Moscow , Russia.|c LIA 1066 French-Russian Joint Cancer Research Laboratory , Villejuif , France.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Razin
authors.affiliation: a Institute of Gene Biology, Russian Academy of Sciences , Moscow , Russia.|b Department of Molecular Biology , Lomonosov Moscow State University , Moscow , Russia.|c LIA 1066 French-Russian Joint Cancer Research Laboratory , Villejuif , France.
authors.forename: Omar L
authors.initials: OL
authors.lastname: Kantidze
mesh_terms: D016922:Cellular Senescence; D018385:Centrosome / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication; D006358:Hot Temperature; D006801:Humans; D016196:S Phase; D014404:Tubulin / Q000378:metabolism
chemical_list: D014404:Tubulin
keywords: DNA damage; DNA replication; cell cycle; cellular senescence; centrosome amplification; heat stress; licensing