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Updated: Sep 10, 2025

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CpG Methylation Protects DNA against Ionizing Radiation

Leo Sala1, Tereza Zápotocká1, Jana Šáchová2

  • 1Department of Dynamics of Molecules and Clusters, J. Heyrovský Institute of Physical Chemistry of the CAS, Dolejškova 3, 182 23 Prague, Czech Republic.

The Journal of Physical Chemistry. B
|August 20, 2025
PubMed

Insights

DNA methylation offers protection against ionizing radiation damage. Even a few methylated CpG sites reduce DNA lesions from low- and high-LET radiation, impacting cancer radiotherapy.

Area of Science:

  • Epigenetics
  • Radiation Biology
  • Nanotechnology

Background:

  • DNA methylation is a crucial epigenetic regulator, and its disruption is linked to diseases like cancer.
  • Cellular DNA methylation levels may influence cancer cell response to radiotherapy.
  • The direct impact of DNA methylation on radiation-induced DNA damage is not fully understood.

Purpose of the Study:

  • To investigate the effect of DNA methylation on DNA damage from ionizing radiation in a cell-free system.
  • To determine if DNA methylation provides a protective effect against radiation-induced DNA lesions.

Main Methods:

  • Utilized DNA origami nanotechnology to create precisely methylated DNA structures.
  • Exposed methylated and unmethylated DNA to low-LET (electron) and high-LET (carbon ion) radiation.
  • Quantified DNA lesions using quantitative Polymerase Chain Reaction (qPCR).
  • Observed DNA double-strand breaks using Atomic Force Microscopy (AFM) on DNA origami nanoframes.

Main Results:

  • Methylated DNA exhibited a reduced number of DNA lesions compared to unmethylated DNA under both low- and high-LET irradiation.
  • AFM single-molecule observations indicated fewer double-strand breaks in methylated DNA after carbon ion irradiation.
  • Even a small number of methylated CpG sites conferred a protective effect.

Conclusions:

  • DNA methylation provides a radioprotective effect on DNA in solution.
  • This methylation-induced radioprotection may influence the differential radiation response observed in cellular DNA.
  • Findings should be considered when evaluating DNA radiation damage yields and predicting radiotherapy outcomes.

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