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

Szymonowicz, Klaudia Anna; Krysztofiak, Adam; van der Linden, Jansje; Kern, Ajvar; Deycmar, Simon;
GND
1128825643
VIAF
6127149108416068780007
ORCID
0000-0001-9695-8771
Affiliation
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA, sebastian.oeck@uk-essen.de
Oeck, Sebastian;
GND
1231513799
LSF
55957
Squire, Anthony; Koska, Benjamin; Hlouschek, Julian; Vüllings, Melanie;
GND
1231454032
Affiliation
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany, christian.neander@uk-essen.de
Neander, Christian;
GND
123603498
ORCID
0000-0002-8772-4778
LSF
59282
Affiliation
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany, jens.siveke@uk-essen.de
Siveke, Jens T.; Matschke, Johann; Pruschy, Martin;
GND
122476190
LSF
53000
Affiliation
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany, beate.timmermann@uk-essen.de
Timmermann, Beate;
GND
1210960990
ORCID
0000-0003-1058-2107
LSF
49484
Affiliation
Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany, verena.jendrossek@uni-due.de
Jendrossek, Verena

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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Szymonowicz, K., Krysztofiak, A., van der Linden, J., Kern, A., Deycmar, S., Oeck, S., Squire, A., Koska, B., Hlouschek, J., Vüllings, M., Neander, C., Siveke, J.T., Matschke, J., Pruschy, M., Timmermann, B., Jendrossek, V., 2020. Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining. https://doi.org/10.3390/cells9040889
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