Origin of overstretching transitions in single-stranded nucleic acids

Area of Science:

• Biophysics
• Molecular Biology
• Structural Biology

Background:

• Single-stranded nucleic acids (DNA and RNA) display complex mechanical behaviors under force.
• Understanding overstretching transitions is crucial for elucidating molecular elasticity and function.

Purpose of the Study:

• To investigate the molecular mechanisms underlying overstretching transitions in single-stranded DNA and RNA.
• To identify the structural changes responsible for force-induced transitions in nucleic acid helices.

Main Methods:

• Combined single-molecule force spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and molecular mechanics simulations.
• Analyzed force-induced transitions in polydeoxyadenylic acid (ssDNA) and polyadenylic acid (ssRNA).

Main Results:

• Identified a low-force transition involving helical unwinding and base unstacking in both ssDNA and ssRNA.
• Determined that the high-force transition in ssDNA is driven by a cooperative flip of the backbone γ torsion within the B-type helix.
• Observed that the γ torsion flip in A-type helices is less cooperative and does not produce a high-force plateau.
• Induced a similar high-force transition in ssRNA using urea, suggesting disruption of backbone hydrogen bonding.

Conclusions:

• The cooperative flip of the γ torsion is a key mechanism for high-force transitions in B-type nucleic acid helices.
• Structural differences between A-type and B-type helices influence the cooperativity of force-induced transitions.
• Hypothesized that a similar γ torsion flip mechanism contributes to the elasticity of double-stranded DNA.