in vitro, in vivo Characterization of Structure-Based Nucleosome Binding Peptides

Abstract

Most DNA in-vivo is strongly bent, including in the nucleosome. Experimental evidence on cyclization of DNA fragments shorter than 100 base-pairs points to the fact that strongly bent DNA --most relevant from a biological perspective --is considerably moreflexible than expected. We propose a general quantitative framework of polymer deformation, Energy Convex Hull (ECH), which includes both the weak and strong bending regimes on the same footing, based on a single physical principle. As the bending deformation increases beyond a certain (polymer-specific) point, the change in the convexity properties of the effective deformation energy of the polymer makes the harmonic deformation energetically unfavorable: in this strong bending regime the energy of the polymer varies linearly with the average deformation, as the system follows the convex hull of the deformation energy function. As a result, the energy of strongly bent DNA is effectively lowered, the bending proceeds via two ''phases'': strongly bent(kinks) and weekly bent. Predictions of ECH are verified againstrecent experiments on DNA cyclization. Counter-intuitively, cyclization probability of very short DNA loops is predicted to increase with decreasing loop length. We use ECH to gain insights into the energetic and structural aspects of strongly bent DNA in the nucleosome.