Sensitivity of DNA Looping to Sequence-dependent Stiffness

Poster Presentation in Biophysical Society Meeting, Baltimore

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Protein-mediated DNA looping plays an important role in gene regulation. Empirically it is known that sequence-dependent mechanical effect such as intrinsic bends or softer regions in the substrate DNA affect loop formation, but quantitative models are lacking. We employ a continuum rod model to simulate protein-mediated DNA looping as a means to explore how the sequence maps to the overall structural properties of the duplex. The model includes sequence-dependent intrinsic curvature, chirality, and stiffness. We address the fundamental question of how sequence-dependent stiffness influences the looping of DNA bound to regulatory proteins like the lactose repressor. We report two major findings: First, any non-uniform stiffness tends to lower the energetic cost of looping. Second, the deformation tends to localize in ‘softer’ regions which in turn affects the loop topology as characterized by twist and writhe. The model also offers the capability to calibrate and benchmark experimental measurements of sequence-dependent stiffness.


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