Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 13, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2119132119
Keywords
clustered DNA damage; atomic force microscopy; ionizing radiation; DNA repair
Categories
Funding
- Research Project with Heavy Ions at QST-Heavy Ion Medical Accelerator in Chiba
- Ministry of Education, Culture, Sports, Science and Technology [21K12248, 16H02959, 18H03374]
- Grants-in-Aid for Scientific Research [18H03374, 21K12248, 16H02959] Funding Source: KAKEN
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This study established a method to evaluate the yield and complexity of clustered DNA damage in irradiated cells using atomic force microscopy. It was found that clustered DNA damage is a signature of ionizing radiation, and Fe ion beams produce clustered DNA damage with high complexity.
Clustered DNA damage is related to the biological effects of ionizing radiation. However, its precise yield and complexity (i.e., number of lesions per damaged site) in vivo remain unknown. To better understand the consequences of clustered DNA damage, a method was established to evaluate its yield and complexity in irradiated cells by atomic force microscopy. This was achieved by isolating and concentrating damaged DNA fragments from purified genomic DNA. It was found that X-rays and Fe ion beams caused clustered DNA damage in human TK6 cells, whereas Fenton's reagents did it less efficiently, highlighting clustered DNA damage as a signature of ionizing radiation. Moreover, Fe ion beams produced clustered DNA damage with high complexity. Remarkably, 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 the lethal effect of complex DSBs.
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