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DNA bubbles and bending : how conformational fluctuations modify its thermal denaturation

par Manoel Manghi - 21 septembre 2007

The denaturation of the DNA polymer is a physical process in the course of which the double strand, or helix, can open locally thanks to thermal fluctuations. An opening of successive base pairs creates a denaturation bubble. Within a bubble the two fluctuating single strands have a bending rigidity 50 times weaker than that of the unopened helix. It follows that at a given temperature, DNA can explore a much larger number of geometrical configurations when in the bubble state and therefore increase its conformational entropy. In this way, it can also have a higher local curvature, for example when wrapped around a histone. The external DNA geometry will in turn influence the bubble creation process. This mutual influence naturally leads to a theoretical model coupling the local internal DNA states (open or closed base pairs) and the local curvature of the DNA chain.

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Fraction of open base pairs as a function of temperature for simple synthetic DNA, composed of 1815 base pairs [one strand is made up of one type of base, adenine (A), and the other, thymine (T)]. The symbols correspond to experimental data and the theoretical curve is fitted with only two adjustable parameters. Typical configurations of double stranded DNA are schematized for different temperatures, showing the different “stages” of its denaturation. Close to the melting temperature, where the fraction is equal to 0.5, we have shown a configuration with a denaturation bubble near the center of the polymer.

We have formulated such a coupled DNA model and solved it exactly using standard tools of statistical physics. This internal-external coupling, which was not previously taken into account in DNA physics modelling, allows one to address and answer a whole class of still open problems in this field. For example, it permits one to calculate as a function of microscopic parameters the denaturation, or melting, temperature above which the double strand tends to a completely open state. In contrast, this temperature was introduced into most previous statistical models of DNA denaturation by hand in order to analyse experimental results. Our coupled model can also be used to both calculate the typical size of DNA, or radius of gyration, as a function of temperature (whether rigid or crumpled) and account for finite size effects that are all important even for DNA polymers as long as several thousand base pairs. Understanding the physics of DNA, and more particularly denaturation bubbles, is an important challenge for biology, because a large number of biological mechanisms, like compaction, replication, transcription, and protein pinning, intimately depend on it.

Details are given in the corresponding paper Thermal Denaturation of Fluctuating DNA Driven by Bending Entropy published in J. Palmeri, M. Manghi, and N. Destainville, Physical Review Letters 99, 088103 (2007). The corresponding author is John Palmeri.