Chromatin Trapping of Factors Involved in DNA Replication and Repair Underlies Heat-Induced Radio- and Chemosensitization
| Autor: | Sergey V. Razin, Bogdan Avanesyan, Omar L. Kantidze, Georgij Arapidi, Artem V. Luzhin, Polina V Shnaider, V. O. Shender, Nadezhda V. Petrova, Igor I. Kireev, Artem K. Velichko, Natalia Ovsyannikova |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Poly Adenosine Diphosphate Ribose Hot Temperature DNA repair DNA damage Poly ADP ribose polymerase DNA replication Article PARP 03 medical and health sciences 0302 clinical medicine Chemosensitization Humans lcsh:QH301-705.5 Okazaki fragments Chemistry Nuclear Proteins General Medicine DNA hyperthermia Cell biology Chromatin 030104 developmental biology HEK293 Cells lcsh:Biology (General) 030220 oncology & carcinogenesis Cancer cell chromatin Poly(ADP-ribose) Polymerases DNA Damage HeLa Cells |
| Zdroj: | Cells, Vol 9, Iss 1423, p 1423 (2020) Cells Volume 9 Issue 6 |
| ISSN: | 2073-4409 |
| Popis: | Hyperthermia has been used as an adjuvant treatment for radio- and chemotherapy for decades. In addition to its effects on perfusion and oxygenation of cancer tissues, hyperthermia can enhance the efficacy of DNA-damaging treatments such as radiotherapy and chemotherapy. Although it is believed that the adjuvant effects are based on hyperthermia-induced dysfunction of DNA repair systems, the mechanisms of these dysfunctions remain elusive. Here, we propose that elevated temperatures can induce chromatin trapping (c-trapping) of essential factors, particularly those involved in DNA repair, and thus enhance the sensitization of cancer cells to DNA-damaging therapeutics. Using mass spectrometry-based proteomics, we identified proteins that could potentially undergo c-trapping in response to hyperthermia. Functional analyses of several identified factors involved in DNA repair demonstrated that c-trapping could indeed be a mechanism of hyperthermia-induced transient deficiency of DNA repair systems. Based on our proteomics data, we showed for the first time that hyperthermia could inhibit maturation of Okazaki fragments and activate a corresponding poly(ADP-ribose) polymerase-dependent DNA damage response. Together, our data suggest that chromatin trapping of factors involved in DNA repair and replication contributes to heat-induced radio- and chemosensitization. |
| Databáze: | OpenAIRE |
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