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@ARTICLE{Schwan:364933,
author = {Schwan, Laura and Averbeck, Nicole B. and Durante, Marco
and Jakob, Burkhard},
title = {{B}ase-excision repair increases {DNA} double-strand break
clustering within heavy-ion tracks and modulates repair at
δ-electron-induced breaks},
journal = {Scientific reports},
volume = {16},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Springer Nature},
reportid = {GSI-2026-00302},
pages = {1339},
year = {2026},
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/."},
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.},
keywords = {DNA Breaks, Double-Stranded: radiation effects / DNA
Repair: radiation effects / Humans / Electrons: adverse
effects / Heavy Ions: adverse effects / DNA-(Apurinic or
Apyrimidinic Site) Lyase: metabolism / DNA-(Apurinic or
Apyrimidinic Site) Lyase: antagonists $\&$ inhibitors / DNA
Glycosylases: metabolism / DNA Glycosylases: antagonists
$\&$ inhibitors / Histones: metabolism / Excision Repair /
Clustered DNA-damage (Other) / DNA repair (Other) / DNA-end
resection (Other) / Heavy ions (Other) / Space radiation
(Other) / δ-electrons (Other) / DNA-(Apurinic or
Apyrimidinic Site) Lyase (NLM Chemicals) / DNA Glycosylases
(NLM Chemicals) / APEX1 protein, human (NLM Chemicals) /
oxoguanine glycosylase 1, human (NLM Chemicals) / Histones
(NLM Chemicals)},
cin = {BIO},
ddc = {600},
cid = {I:(DE-Ds200)BIO-20160831OR354},
pnm = {633 - Life Sciences – Building Blocks of Life: Structure
and Function (POF4-633) / FAIR Phase-0 - FAIR Phase-0
Research Program (GSI-FAIR-Phase-0) / SUC-GSI-Darmstadt -
Strategic university cooperation GSI-TU Darmstadt
(SUC-GSI-DA)},
pid = {G:(DE-HGF)POF4-633 / G:(Ds200)GSI-FAIR-Phase-0 /
G:(DE-Ds200)SUC-GSI-DA},
experiment = {EXP:(DE-Ds200)SESA-20200803},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41513727},
UT = {WOS:001660886800005},
doi = {10.1038/s41598-025-32823-z},
url = {https://repository.gsi.de/record/364933},
}