DNA double strand break repair inhibition as a cause of heat radiosensitization: re-evaluation considering backup pathways of NHEJ

International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
George IliakisMinli Wang

Abstract

Heat shock is one of the most effective radiosensitizers known. As a result, combination of heat with ionizing radiation (IR) is considered a promising strategy in the management of human cancer. The mechanism of heat radiosensitization has been the subject of extensive work but a unifying mechanistic model is presently lacking. To understand the cause of excessive death in irradiated cells after heat exposure, it is necessary to characterize the lesion(s) underlying the effect and to determine which of the pathways processing this lesion are affected by heat. Since DNA double strand breaks (DSBs) are the main cause for IR-induced cell death, inhibition of DSB processing has long been considered a major candidate for heat radiosensitization. However, effective radiosensitization of mutants with defects in homologous recombination repair (HRR), or in DNA-PK dependent non-homologous end joining (D-NHEJ), the two primary pathways of DSB repair, has led to the formulation of models excluding DSBs as a cause for this phenomenon and attributing heat radiosensitization to inhibition of base damage processing. Since direct evidence for a major role of base damage in heat radiosensitization, or in IR-induced killing for that matter, is ...Continue Reading

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Citations

May 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Przemek M KrawczykJacob A Aten
Feb 28, 2014·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Makoto IharaTakeo Ohnishi
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Aug 25, 2016·Oncotarget·Arlene L OeiNicolaas A P Franken
Apr 22, 2016·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Antoine G van der Heijden, Mark W Dewhirst
May 26, 2017·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Arlene L OeiNicolaas A P Franken
Jun 8, 2017·International Journal of Molecular Sciences·Nadine SchulzCarla Rohrer Bley
Dec 17, 2016·Journal of Therapeutic Ultrasound·Giovanni BorasiMaria Carla Gilardi
Jul 23, 2020·Computational and Mathematical Methods in Medicine·Mathias S WeylandStephan Scheidegger
Aug 4, 2021·Journal of Experimental Botany·Shin-Hee HanChung-Mo Park

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