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CpG Methylation Protects DNA against Ionizing Radiation

L. Sala,Tereza Zápotocká,J. Šáchová,Václav Olšanský,David Chvatil,François Chevalier,Violaine Vizcaino,Alain Mery,J. Kočišek

Published 2025 in Journal of Physical Chemistry B

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.

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