Thesis : Anil Kumar DASANNA (LPT). September 2013

Closure of DNA denaturation bubbles coupled to DNA elasticity

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Abstract : The physical understanding of biological processes such as transcription requires the knowledge of double-stranded DNA (dsDNA) physics. A notable thermodynamic property of dsDNA is its denaturation, at the melting temperature, in which it unwinds into two single-stranded DNAs via the formation of denaturation bubbles (segment of consecutive unpaired base-pairs). The dynamics of denaturation has been studied so far at the base-pair (bp) scale, ignoring conformational chain degrees of freedom. These studies do not explain the very long closure times of 20 to 100 microseconds, measured by Altan-Bonnet et al., of 18 bps long bubbles at room temperature. In this thesis, I studied the closure of pre-equilibrated large bubbles, by using Brownian dynamics simulations of two simple DNA coarse- grained models. I will show that the closure occurs via two steps : first, a fast zipping of the initial bubble occurs until a meta-stable state is reached, due to the large bending and twisting energies stored in the bubble. Then, the meta-stable bubble closes either via rotational diffusion of the stiff side arms until their alignment, or bubble diffusion until it reaches the chain end, or locally by thermal activation, depending on the DNA length and elastic moduli. I will show that the physical mechanism behind these long timescales is therefore the dynamical coupling between base-pair and chain degrees of freedom.

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