Formation of clustered DNA damage in vivo upon irradiation with ionizing radiation: Visualization and analysis with atomic force microscopy.

Toshiaki Nakano, Ken Akamatsu, Masataka Tsuda, Ayane Tujimoto, Ryoichi Hirayama, Takeshi Hiromoto, Taro Tamada, Hiroshi Ide, Naoya Shikazono

Proceedings of the National Academy of Sciences of the United States of America 2022 Mar 29

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SignificanceDNA damage causes loss of or alterations in genetic information, resulting in cell death or mutations. Ionizing radiations produce local, multiple DNA damage sites called clustered DNA damage. In this study, a complete protocol was established to analyze the damage complexity of clustered DNA damage, wherein damage-containing genomic DNA fragments were selectively concentrated via pulldown, and clustered DNA damage was visualized by atomic force microscopy. It was found that X-rays and Fe ion beams caused clustered DNA damage. Fe ion beams also produced clustered DNA damage with high complexity. Fe ion beam-induced complex DNA double-strand breaks (DSBs) containing one or more base lesion(s) near the DSB end were refractory to repair, implying their lethal effects.

Citation

Toshiaki Nakano, Ken Akamatsu, Masataka Tsuda, Ayane Tujimoto, Ryoichi Hirayama, Takeshi Hiromoto, Taro Tamada, Hiroshi Ide, Naoya Shikazono. Formation of clustered DNA damage in vivo upon irradiation with ionizing radiation: Visualization and analysis with atomic force microscopy. Proceedings of the National Academy of Sciences of the United States of America. 2022 Mar 29;119(13):e2119132119