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Precise Mechanochemical Scission of DNA Guided by Secondary Structures
Johannes Hahmann1,2,3, Arjuna Selvakumar1,2, Boris N Schüpp3,4
1Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany.
Journal of the American Chemical Society
|March 25, 2026
Summary
DNA hairpins act as novel biomechanophores, precisely directing DNA strand scission. This discovery enhances DNA manipulation tools through controlled mechanical force and sequence specificity.
Area of Science:
- Biochemistry
- Molecular Biology
- Biophysics
Background:
- DNA is a versatile biopolymer for mechanochemistry.
- Existing methods using nicks have limited precision due to base fraying.
Purpose of the Study:
- To investigate DNA hairpins as novel biomechanophores for precise DNA scission.
- To explore the mechanism of mechanically induced cleavage directed by DNA hairpins.
Main Methods:
- Utilized double-stranded DNA (dsDNA) constructs with embedded hairpin motifs.
- Applied ultrasonication to induce mechanical stress and cleavage.
- Employed all-atom molecular dynamics (MD) simulations to analyze force localization.
- Used next-generation sequencing (NGS) to characterize scission patterns.
Main Results:
- Ultrasonication induced regioselective cleavage opposite the hairpin loop in dsDNA.
- MD simulations showed force concentration on the nonhairpin strand.
- NGS revealed a narrow scission distribution on the nonhairpin strand, distinct from the hairpin strand.
- A two-step cleavage mechanism was supported by simulation and sequencing data.
Conclusions:
- DNA hairpins function as the first biomechanophores for precise, mechanically induced DNA strand scission.
- This finding expands the capabilities of nucleic acid manipulation through mechanochemistry.
- The study establishes a new paradigm for controlling DNA cleavage with high spatial accuracy.
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