Visualizing Reactive Oxygen Species-Induced DNA Damage Process in Higher-Ordered Origami Nanostructures

Area of Science:

• Biochemistry
• Nanotechnology
• Molecular Biology

Background:

• Cellular genetic information is organized into complex, higher-ordered DNA structures within the nucleus.
• Understanding DNA's structural dynamics is crucial for elucidating its functional mechanisms.

Purpose of the Study:

• To simulate nucleosome DNA compaction and stacking density using DNA framework nanostructures (DFNs).
• To investigate the dynamic structural changes, reaction kinetics, and preferential reaction sites of DFNs during reactive oxygen species (ROS) interactions.
• To develop advanced analytical methods for studying nuclear DNA structural dynamics.

Main Methods:

• Development of DNA framework nanostructures (DFNs) as model systems.
• Utilization of atomic force microscopy-based single-particle analysis (SPA) for data reconstruction and imaging.
• Analysis of geometric morphology, local mechanical stress, and base distribution influencing DFN kinetics.

Main Results:

• DFN geometric morphology was found to constrain reaction kinetics with ROS.
• Local mechanical stress and regional base distribution were identified as key factors governing DFN-ROS interactions.
• A reaction process diagram detailing ROS-DFN interactions, intermediate products, and activation energies was generated.

Conclusions:

• The study provides novel insights into the dynamic structural changes of highly folded DNA within the nucleus.
• The developed SPA method offers a powerful tool for analyzing DNA structural domains.
• Findings contribute to understanding the mechanisms behind functional differences in topologically associating domains.