Sequence-Dependent Persistence Length of Long DNA

Abstract

Using a high-throughput genome mapping approach, we have obtained circa 50 million measurements of the extension of internal human DNA segments in a 41 nm × 41 nm nanochannel. The underlying DNA sequences, obtained by mapping to the reference human genome, are 2.5 to 393 kilobase pairs long and contain % GC contents between 32.5% and 60%. Using Odijk’s theory for a channel-confined wormlike chain, these data reveal that the DNA persistence length increases by almost 20% as the % GC content increases. The increased persistence length is rationalized by a model, containing no adjustable parameters, that treats the DNA as a statistical terpolymer with a sequence-dependent intrinsic persistence length and a sequence-independent electrostatic persistence length.

Distribution of label spacings for genome mapping in nanochannels

“…3 show the comparison for the widest channel measured, for contour-length separations L = 53125 bp and 28125 bp. We estimate that these values correspond to L = 18 µm and 9.6 µm, assuming that the low intercalation used in these experiments does not affect L. 41 We observe excellent agreement between theory and experiment. The hashed regions indicate the difference between the Gaussian approximation and the full theory, it corresponds to the contributions of hairpins shortening the conformations.…”

“…This means that the typical hairpins are quite short, typically much shorter than the 2500 bp (850 nm) lower bound for resolving nearest-neighbor fluorescent labels in experiments. 41 This is an important observation because the experimental data were conditioned on the sequence of fluorescent labels. 29 Conformations that did not agree with the order of labels obtained from a reference genome were discarded.…”

“…Second, the sensitive dependence of the predicted distribution upon channel size can test theories for the effective channel width,40 an important open question for genome mapping experiments. We further expect that the tails are sensitive to flexibility of the DNA backbone, providing a probe for sequence-specific effects on confined DNA conformations, an emerging area of interest 41. Finally, an entirely open question is to understand the conformational dynamics [42][43][44][45][46].…”

Phosphorylated CtIP bridges DNA to promote annealing of broken ends

“…A preferred binding to AT-rich DNA might reflect the need for CtIP to partially open the DNA helix to facilitate binding, which would be easier in AT-rich regions that are less stable and more prone to melting (43). In addition, the persistence length of DNA increases by up to 20% as the GC content of DNA increases, which also might contribute to the observed selectivity for the softer AT-rich regions (44).…”

Stretching Wormlike Chains in Narrow Tubes of Arbitrary Cross-Sections

“…The statistical behaviors of semiflexible polymers confined in nano-and micro-tubes are fundamental problems in polymer physics and have been investigated both experimentally and theoretically for decades [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. A thorough understanding of these problems is very important in the development of various application techniques that exploit the effects of confinement and stretching on polymers, including genome mapping [15,16], DNA sorting [17], and DNA denaturation mapping [18,19], etc.…”