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- Title
Chromatin Trapping of Factors Involved in DNA Replication and Repair Underlies Heat-Induced Radio- and Chemosensitization.
- Authors
Luzhin, Artem V.; Avanesyan, Bogdan; Velichko, Artem K.; Shender, Victoria O.; Ovsyannikova, Natalia; Arapidi, Georgij P.; Shnaider, Polina V.; Petrova, Nadezhda V.; Kireev, Igor I.; Razin, Sergey V.; Kantidze, Omar L.
- Abstract
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.
- Subjects
DNA repair; DNA replication; CHROMATIN; POLY ADP ribose; PROTEOMICS; TREATMENT effectiveness; DNA damage
- Publication
Cells (2073-4409), 2020, Vol 9, Issue 6, p1423
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells9061423