Strand diffusion-limited closure of denaturation bubbles in DNA

TL;DR

This study investigates the slow closure of DNA denaturation bubbles, revealing that chain bending and rotational diffusion of dsDNA arms dominate the final closure step, with long timescales scaling as N^2.4.

Contribution

It introduces a combined simulation and analytical model highlighting the importance of chain bending and rotational diffusion in DNA bubble closure dynamics.

Findings

Closure times scale as N^2.4.

Closure halts at a bent metastable state of ~10 bp.

Final closure is controlled by dsDNA arm rotational diffusion.

Abstract

The closure dynamics of a pre-equilibrated DNA denaturation bubble is studied using both Brownian dynamics simulations and an analytical approach. The numerical model consists of two semi-flexible interacting single strands (ssDNA) and a bending modulus which depends on the base-pair state, with double-strand DNA (dsDNA) segments being 50 times stiffer than ssDNA ones. For DNA lengths from N=20 to 100 base-pairs (bp) and initial bubble sizes of N-6 bp, long closure times of 0.1 to 4 microseconds are found, following a scaling law in N^2.4. The bubble starts to close by a fast zipping which stops when the bubble reaches a highly bent metastable state of length around 10 bp. The limiting final step to complete closure is controlled by the dsDNA "arms" rotational diffusion, with closure occurring once they are nearly aligned. The central role of chain bending, which cannot be accounted for in one-dimensional models, is thus illuminated.