Nanomechanics of negatively supercoiled diaminopurine-substituted DNA

• Published in: Nucleic acids research 2021-11, Vol.49 (20), p.11778-11786
• Main Authors: Salerno, Domenico, Marrano, Claudia Adriana, Cassina, Valeria, Cristofalo, Matteo, Shao, Qing, Finzi, Laura, Mantegazza, Francesco, Dunlap, David
• Format: Article
• Language: English
• Subjects: 2-Aminopurine - analogs & derivatives; DNA, Superhelical - chemistry; Molecular Biology; Molecular Dynamics Simulation
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkab982

Abstract Single molecule experiments have demonstrated a progressive transition from a B- to an L-form helix as DNA is gently stretched and progressively unwound. The particular sequence of a DNA segment defines both base stacking and hydrogen bonding that affect the partitioning and conformations of the two phases. Naturally or artificially modified bases alter H-bonds and base stacking and DNA with diaminopurine (DAP) replacing adenine was synthesized to produce linear fragments with triply hydrogen-bonded DAP:T base pairs. Both unmodified and DAP-substituted DNA transitioned from a B- to an L-helix under physiological conditions of mild tension and unwinding. This transition avoids writhing and the ease of this transition may prevent cumbersome topological rearrangements in genomic DNA that would require topoisomerase activity to resolve. L-DNA displayed about tenfold lower persistence length than B-DNA. However, left-handed DAP-substituted DNA was twice as stiff as unmodified L-DNA. Unmodified DNA and DAP-substituted DNA have very distinct mechanical characteristics at physiological levels of negative supercoiling and tension.