Journal Article

GSI-2026-00302

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Base-excision repair increases DNA double-strand break clustering within heavy-ion tracks and modulates repair at δ-electron-induced breaks

Schwan, L. (First author)GSI* ; Averbeck, N. B. (Corresponding author)GSI* ; Durante, M.GSI* ; Jakob, B. (Last author)GSI*

2026
Springer Nature [London]

Please use a persistent id in citations: doi:10.1038/s41598-025-32823-z  doi:10.15120/GSI-2026-00302

Abstract: Space radiation poses a threat to human health during space missions. Its biological effect largely depends on heavy ions. These induce highly clustered DNA damage along their tracks, which is difficult to repair. If this damage is not repaired correctly, or not at all, mutations and possibly cancer can occur in the long term. δ-electrons induced by fast heavy ions lead to further DNA damage outside ion tracks, resembling that of sparsely-ionising radiation. Using inhibitors of the crucial base-excision repair factors OGG1 and APE1, we show that the repair of DNA base-lesions within heavy-ion tracks causes DNA double-strand breaks (DSBs), which increases difficult-to-repair in-track DSB clustering. We further found that DSBs induced by δ-electrons of fast heavy ions are more often decorated by the resection factor RPA, which suggests that they are more often repaired in a resection-dependent manner than X-ray-induced DSBs, despite their resemblance. Using γH2AX assays to assess DSB repair kinetics, we found that δ-electron-induced DSBs are repaired faster than those induced by X-rays in G1-phase cells, despite the fact that δ-electron-induced DSBs are frequently resected, which typically entails slower repair processes. These findings on δ-electron-induced DSBs imply that the quantity of clustered DSBs in irradiated cells affects the overall response of cells to DNA-damage. Based on our results on base-excision repair and the processing of δ-electron-induced DSBs, we conclude that the interplay between DNA-damage repair processes is a pivotal factor in the course of DNA repair and, consequently, genomic integrity.

Keyword(s): DNA Breaks, Double-Stranded: radiation effects (MeSH) ; DNA Repair: radiation effects (MeSH) ; Humans (MeSH) ; Electrons: adverse effects (MeSH) ; Heavy Ions: adverse effects (MeSH) ; DNA-(Apurinic or Apyrimidinic Site) Lyase: metabolism (MeSH) ; DNA-(Apurinic or Apyrimidinic Site) Lyase: antagonists & inhibitors (MeSH) ; DNA Glycosylases: metabolism (MeSH) ; DNA Glycosylases: antagonists & inhibitors (MeSH) ; Histones: metabolism (MeSH) ; Excision Repair (MeSH) ; Clustered DNA-damage ; DNA repair ; DNA-end resection ; Heavy ions ; Space radiation ; δ-electrons ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; DNA Glycosylases ; APEX1 protein, human ; oxoguanine glycosylase 1, human ; Histones

Note: grant 50WB2014 and the European Space Agency, grant AO-2019-IBER_005. "This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/."

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Contributing Institute(s):

1. Biophysik (BIO)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. FAIR Phase-0 - FAIR Phase-0 Research Program (GSI-FAIR-Phase-0) (GSI-FAIR-Phase-0)
3. SUC-GSI-Darmstadt - Strategic university cooperation GSI-TU Darmstadt (SUC-GSI-DA) (SUC-GSI-DA)

Experiment(s):

1. SESA: ESA Experiments at SIS (POF4-633; HTA)

Appears in the scientific report 2026

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