Physics of base-pairing dynamics in DNA

Abstract

As a key molecule of Life, Deoxyribonucleic acid (DNA) is the focus of numbers of investigations with the help of biological, chemical and physical techniques. From a physical point of view, both experimental and theoretical works have brought quantitative insights into DNA base-pairing dynamics that we review in this Report, putting emphasis on theoretical developments. We discuss the dynamics at the base-pair scale and its pivotal coupling with the polymer one, with a polymerization index running from a few nucleotides to tens of kilo-bases. This includes opening and closure of short hairpins and oligomers as well as zipping and unwinding of long macromolecules. We review how different physical mechanisms are either used by Nature or utilized in biotechnological processes to separate the two intertwined DNA strands, by insisting on quantitative results. They go from thermally-assisted denaturation bubble nucleation to force- or torque- driven mechanisms. We show that the helical character of the molecule, possibly supercoiled, can play a key role in many denaturation and renaturation processes. We categorize the mechanisms according to the relative timescales associated with base-pairing and chain degrees of freedom such as bending and torsional elastic ones. In some specific situations, these chain degrees of freedom can be integrated out, and the quasi- static approximation is valid. The complex dynamics then reduces to the diffusion in a low-dimensional free-energy landscape. In contrast, some important cases of experimental interest necessarily appeal to far-from-equilibrium statistical mechanics and hydrodynamics.Comment: Review Article, revised versio

Possible scenarios of DNA double-helix unzipping process in single-molecule manipulation experiments

“…At high pulling speeds (>1µm/sec) the process becomes to be non-equilibrium, about what argues the hysteresis occurrence on the force-distance curve [17]. In this case the rotational friction torque starts to play a significant role [8,17] and pairs do not have time to transit into the metastable state. In this case only the second scenario can take place when base pairs open along the 'stretch' pathway which has much higher vibrational frequency than the 'opening' pathway.…”

“…These methods use optical tweezers [2], microneedles [3], atomic force microscopes [5]. Single-molecule micromanipulation methods allow to study processes such as DNA stretching, bending, twisting [4,6,7] and the DNA double helix nucleic base pairs opening [3,8,[15][16][17][18][19]. Among them especially important is the process of sequential separation of nucleic bases in DNA base pairs under the action of external forces (DNA unzipping), which plays a key role in the genetic information transferring process.…”

Statistical physics and mesoscopic modeling to interpret tethered particle motion experiments

“…This method can in principle be used to detect any transient DNA-protein complex formation and dwell-times. Similar approaches have been used to study DNA hairpins opening/closure [91] and DNA G-quadruplex unfolding/refolding [92].…”

A polymer model of bacterial supercoiled DNA including structural transitions of the double helix

“…Explicit polymer models can be further divided into two types. Depending on the addressed question, structural details can indeed be coarse-grained at the scale of a single nucleotide [32,35] or at a larger scale of a few tens base pairs [29,30,31,36]. Single nucleotide resolution models have thus been useful to investigate properties of small (i.e.…”