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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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Autores principales: Szymonowicz, Klaudia, Krysztofiak, Adam, van der Linden, Jansje, Kern, Ajvar, Deycmar, Simon, Oeck, Sebastian, Squire, Anthony, Koska, Benjamin, Hlouschek, Julian, Vüllings, Melanie, Neander, Christian, Siveke, Jens T., Matschke, Johann, Pruschy, Martin, Timmermann, Beate, Jendrossek, Verena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226794/
https://www.ncbi.nlm.nih.gov/pubmed/32260562
http://dx.doi.org/10.3390/cells9040889
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author Szymonowicz, Klaudia
Krysztofiak, Adam
van der Linden, Jansje
Kern, Ajvar
Deycmar, Simon
Oeck, Sebastian
Squire, Anthony
Koska, Benjamin
Hlouschek, Julian
Vüllings, Melanie
Neander, Christian
Siveke, Jens T.
Matschke, Johann
Pruschy, Martin
Timmermann, Beate
Jendrossek, Verena
author_facet Szymonowicz, Klaudia
Krysztofiak, Adam
van der Linden, Jansje
Kern, Ajvar
Deycmar, Simon
Oeck, Sebastian
Squire, Anthony
Koska, Benjamin
Hlouschek, Julian
Vüllings, Melanie
Neander, Christian
Siveke, Jens T.
Matschke, Johann
Pruschy, Martin
Timmermann, Beate
Jendrossek, Verena
author_sort Szymonowicz, Klaudia
collection PubMed
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.
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spelling pubmed-72267942020-05-18 Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining Szymonowicz, Klaudia Krysztofiak, Adam van der Linden, Jansje Kern, Ajvar Deycmar, Simon Oeck, Sebastian Squire, Anthony Koska, Benjamin Hlouschek, Julian Vüllings, Melanie Neander, Christian Siveke, Jens T. Matschke, Johann Pruschy, Martin Timmermann, Beate Jendrossek, Verena Cells Article 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. MDPI 2020-04-05 /pmc/articles/PMC7226794/ /pubmed/32260562 http://dx.doi.org/10.3390/cells9040889 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Szymonowicz, Klaudia
Krysztofiak, Adam
van der Linden, Jansje
Kern, Ajvar
Deycmar, Simon
Oeck, Sebastian
Squire, Anthony
Koska, Benjamin
Hlouschek, Julian
Vüllings, Melanie
Neander, Christian
Siveke, Jens T.
Matschke, Johann
Pruschy, Martin
Timmermann, Beate
Jendrossek, Verena
Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226794/
https://www.ncbi.nlm.nih.gov/pubmed/32260562
http://dx.doi.org/10.3390/cells9040889
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