Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining
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 a...
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doaj-af29afe2eb6a475593fd2b949fb00dd82020-11-25T02:33:57ZengMDPI AGCells2073-44092020-04-01988988910.3390/cells9040889Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End JoiningKlaudia Szymonowicz0Adam Krysztofiak1Jansje van der Linden2Ajvar Kern3Simon Deycmar4Sebastian Oeck5Anthony Squire6Benjamin Koska7Julian Hlouschek8Melanie Vüllings9Christian Neander10Jens T. Siveke11Johann Matschke12Martin Pruschy13Beate Timmermann14Verena Jendrossek15Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyWest German Proton Therapy Centre Essen (WPE), West German Cancer Center (WTZ), University Hospital Essen, 45147 Essen, GermanyDepartment of Radiation Oncology, Laboratory for Applied Radiobiology, University Hospital Zurich, Zurich, SwitzerlandInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Experimental Immunology and Imaging, Imaging Center Essen, University Hospital Essen, 45122 Essen, GermanyWest German Proton Therapy Centre Essen (WPE), West German Cancer Center (WTZ), University Hospital Essen, 45147 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyWest German Proton Therapy Centre Essen (WPE), West German Cancer Center (WTZ), University Hospital Essen, 45147 Essen, GermanyInstitute of Developmental Cancer Therapeutics, West German Cancer Center, University Hospital Essen, Essen, GermanyInstitute of Developmental Cancer Therapeutics, West German Cancer Center, University Hospital Essen, Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyDepartment of Radiation Oncology, Laboratory for Applied Radiobiology, University Hospital Zurich, Zurich, SwitzerlandWest German Proton Therapy Centre Essen (WPE), West German Cancer Center (WTZ), University Hospital Essen, 45147 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyTechnical 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.https://www.mdpi.com/2073-4409/9/4/889ionizing radiationDNA damage fociDNA repairspread-out Bragg peak (SOBP)relative biological effectiveness (RBE)entrance plateau (EP) protons |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining Cells ionizing radiation DNA damage foci DNA repair spread-out Bragg peak (SOBP) relative biological effectiveness (RBE) entrance plateau (EP) protons |
author_facet |
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 |
author_sort |
Klaudia Szymonowicz |
title |
Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining |
title_short |
Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining |
title_full |
Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining |
title_fullStr |
Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining |
title_full_unstemmed |
Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining |
title_sort |
proton irradiation increases the necessity for homologous recombination repair along with the indispensability of non-homologous end joining |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-04-01 |
description |
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. |
topic |
ionizing radiation DNA damage foci DNA repair spread-out Bragg peak (SOBP) relative biological effectiveness (RBE) entrance plateau (EP) protons |
url |
https://www.mdpi.com/2073-4409/9/4/889 |
work_keys_str_mv |
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