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Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining

Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining

Authors :
Klaudia Szymonowicz
Adam Krysztofiak
Jansje van der Linden
Ajvar Kern
Simon Deycmar
Sebastian Oeck
Anthony Squire
Benjamin Koska
Julian Hlouschek
Melanie Vüllings
Christian Neander
Jens T. Siveke
Johann Matschke
Martin Pruschy
Beate Timmermann
Verena Jendrossek
Source :
Cells, Vol 9, Iss 4, p 889 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

Technical improvements in clinical radiotherapy for maximizing cytotoxicity to the tumor while limiting negative impact on co-irradiated healthy tissues include the increasing use of particle therapy (e.g., proton therapy) worldwide. Yet potential differences in the biology of DNA damage induction and repair between irradiation with X-ray photons and protons remain elusive. We compared the differences in DNA double strand break (DSB) repair and survival of cells compromised in non-homologous end joining (NHEJ), homologous recombination repair (HRR) or both, after irradiation with an equal dose of X-ray photons, entrance plateau (EP) protons, and mid spread-out Bragg peak (SOBP) protons. We used super-resolution microscopy to investigate potential differences in spatial distribution of DNA damage foci upon irradiation. While DNA damage foci were equally distributed throughout the nucleus after X-ray photon irradiation, we observed more clustered DNA damage foci upon proton irradiation. Furthermore, deficiency in essential NHEJ proteins delayed DNA repair kinetics and sensitized cells to both, X-ray photon and proton irradiation, whereas deficiency in HRR proteins sensitized cells only to proton irradiation. We assume that NHEJ is indispensable for processing DNA DSB independent of the irradiation source, whereas the importance of HRR rises with increasing energy of applied irradiation.

Details

Language :
English
ISSN :
20734409
Volume :
9
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.f29afe2eb6a475593fd2b949fb00dd8
Document Type :
article
Full Text :
https://doi.org/10.3390/cells9040889