Thermodynamics and kinetics of the B-S transition in base-modified DNA
Artikel i vetenskaplig tidskrift, 2023

Understanding changes in the mechanical properties of nucleic acids is important to understand many biological processes. DNA exhibits a conformational change from canonical B- to overstretched S-form, characterized by 70% elongation, at ∼60–70 pN. The structure of S-form DNA is still debated and also difficult to distinguish from force-induced melting and peeling of DNA. Here, we characterized the kinetics and thermodynamics of the B-S transition and also investigated the effect of base modifications on the transition using tricyclic cytosine tC, which forms hydrogen bonds with guanine and changes the base stacking properties of B-DNA. The B-S transition in 60 bp DNA occurs at ∼63.5 pN (at 1 M salt) and fraying of ∼20 bp precedes the cooperative B-to-S transition of the remaining ∼40 bp. The B-S transition force increases gradually with tC incorporation, whereas the extension and free energy of the transition decrease. We conclude that fewer bp undergo the cooperative B-S transition in tC-stabilized duplexes, due to more fraying of B-DNA at higher transition forces, consistent with the transition becoming faster. For the first time we characterize the kinetics of the cooperative B-to-S transition and it occurs significantly faster than the alternative melting transition, while the extension of B-DNA at the B-to-S transition barrier is almost half-way between B- and S-DNA, suggesting an elastic nature of this transition. By characterizing the free energies of tC-modified relative to unmodified oligos, we estimated that each tC stabilizes the duplex by ∼3 kBT. The approach of studying short synthetic oligonucleotides with modified bases opens up new opportunities for understanding the local structure of nucleic acids with base-pair resolution.

B-S transition

Nucleic acids




Vinoth Sundar Rajan

Chalmers, Life sciences, Kemisk biologi

Sune Levin

Chalmers, Life sciences, Kemisk biologi

M. J. McCauley

Northeastern University

Mark C. Williams

Northeastern University

I. Rouzina

Ohio State University

Marcus Wilhelmsson

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Fredrik Westerlund

Chalmers, Life sciences, Kemisk biologi

Biophysical Journal

0006-3495 (ISSN) 1542-0086 (eISSN)

Vol. 122 3S1



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