CpG Methylation Protects DNA against Ionizing Radiation

Methylation of DNA CpG domains in cellular DNA is a key mechanism of epigenetic regulation. Disruptions in the processes maintaining DNA methylation can lead to diseases like cancer. The radiation response of certain cancer cells may be affected by their DNA methylation levels, which may have consequences in their response to radiotherapy. In this work, we utilized DNA origami nanotechnology to examine whether DNA methylation impacts DNA response to ionizing radiation in solution before biological processes come into play. Our findings reveal that a protective effect is achieved with just a few methylated CpG adducts. Both low-LET (electron) and high-LET (carbon ion) irradiation show a reduced lesion count in methylated DNA, as indicated by qPCR results. AFM single-molecule observations using DNA origami nanoframes suggest fewer double-strand breaks in methylated DNA after carbon ion irradiation. This radioprotective effect may contribute to the differential radiation response of cellular DNA and should be considered when predicting and evaluating DNA radiation damage yields.

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Publication Details

Journal
The Journal of Physical Chemistry B
Published
2025-08-20
DOI
https://doi.org/10.1021/acs.jpcb.5c04043
Primary Topic
Advanced biosensing and bioanalysis techniques
Type
article
Field-Weighted Citation Impact
0.00

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article

CpG Methylation Protects DNA against Ionizing Radiation

David Chvátil, A. Méry, Václav Olšanský, François Chevalier et al.
The Journal of Physical Chemistry B
Advanced biosensing and bioanalysis techniques
article

CpG Methylation Protects DNA against Ionizing Radiation

David Chvátil, A. Méry, Václav Olšanský, François Chevalier, Leo Sala, Jaroslav Kočišek, Violaine Vizcaino, Jana Šáchová, Tereza Zápotocká
article en

Abstract

Methylation of DNA CpG domains in cellular DNA is a key mechanism of epigenetic regulation. Disruptions in the processes maintaining DNA methylation can lead to diseases like cancer. The radiation response of certain cancer cells may be affected by their DNA methylation levels, which may have consequences in their response to radiotherapy. In this work, we utilized DNA origami nanotechnology to examine whether DNA methylation impacts DNA response to ionizing radiation in solution before biological processes come into play. Our findings reveal that a protective effect is achieved with just a few methylated CpG adducts. Both low-LET (electron) and high-LET (carbon ion) irradiation show a reduced lesion count in methylated DNA, as indicated by qPCR results. AFM single-molecule observations using DNA origami nanoframes suggest fewer double-strand breaks in methylated DNA after carbon ion irradiation. This radioprotective effect may contribute to the differential radiation response of cellular DNA and should be considered when predicting and evaluating DNA radiation damage yields.

The Journal of Physical Chemistry BVol. 129(35)
Centre National de la Recherche Scientifique (FR), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR), Normandie Université (FR), Centre de Recherche sur les Ions, les Matériaux et la Photonique (FR), Czech Academy of Sciences, J. Heyrovský Institute of Physical Chemistry (CZ), Czech Academy of Sciences, Institute of Molecular Genetics (CZ), Czech Academy of Sciences, Nuclear Physics Institute (CZ), Université de Caen Normandie (FR)
European Commission, European Cooperation in Science and Technology, Ministerstvo Školství, Mládeže a Tělovýchovy, Central Institute of Medicinal and Aromatic Plants, HORIZON EUROPE European Innovation Council
Openalex Percentile: Top 81%
Advanced biosensing and bioanalysis techniques
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