Sequence-Dependent Mechanics of DNA

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Double-stranded DNA is a semiflexible polymer that can naturally bend on length scales comparable to the size of large DNA-protein complexes like nucleosomes or protein-mediated DNA loops. The sequence of the substrate DNA does not only provide biochemical binding sites for the proteins, but also affects the local mechanical properties of the DNA. Notably, sequence can affect the intrinsic curvature of the DNA, as well as its bendability, or elasticity. While intrinsic bends in DNA and their role in protein-DNA complex formation are well studied, sequence-dependent elasticity still remains only vaguely explored. In order to separate sequence effects on elasticity from those on intrinsic curvature, we have designed sequences of DNA which have nearly identical curvatures but varied AT content and directly measured their mechanical elasticity using constant force axial optical tweezers. We found the persistence length to be highly dependent on the AT content of the DNA, differing almost thirty percent between sequences with nearly identical curvature but different sequence composition. This is a departure from conventional dinucleotide and trinucleotide models, which predict a much smaller difference between the two sequences, but consistent with estimates obtained from the crystallographic structures of protein-DNA complexes.