How a short double-stranded DNA bends

Shin, Jaeoh; Lee, O-Chul; Sung, Wonyong

doi:10.1063/1.4916379

Cited by 13 publications

(12 citation statements)

References 39 publications

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“…This controversial finding spurred debate on the characteristic length at which DNA cyclization efficiency deviates from the predictions of the WLC model. Despite much experimental [5,[17][18][19][20][21] and theoretical effort [7,[22][23][24][25][26][27][28][29][30][31][32][33][34][35], a consensus has not yet been established.…”

Section: Dna Cyclizationmentioning

confidence: 99%

Coarse-Grained Modelling of Extreme DNA Bending

Harrison

Louis

Doye

2014

Biophysical Journal

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DNA cyclization is a powerful technique to gain insight into the nature of DNA bending. The worm-like chain model provides a good description of small to moderate bending fluctuations, but some experiments on strongly-bent shorter molecules suggest enhanced flexibility over and above that expected from the worm-like chain. Here, we use a coarse-grained model of DNA to investigate the thermodynamics of DNA cyclization for molecules with less than 210 base pairs. As the molecules get shorter we find increasing deviations between our computed equilibrium j -factor and the worm-like chain predictions of Shimada and Yamakawa. These deviations are due to sharp kinking, first at nicks, and only subsequently in the body of the duplex. At the shortest lengths, substantial fraying at the ends of duplex domains is the dominant method of relaxation. We also estimate the dynamic j -factor measured in recent FRET experiments. We find that the dynamic j -factor is systematically larger than its equilibrium counterpart, with the deviation larger for shorter molecules, because not all the stress present in the fully cyclized state is present in the transition state. These observations are important for the interpretation of recent experiments, as only kinking within the body of the duplex is genuinely indicative of non-worm-like chain behaviour.

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Section: Dna Cyclizationmentioning

confidence: 99%

Coarse-Grained Modelling of Extreme DNA Bending

Harrison

Louis

Doye

2014

Biophysical Journal

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“…The cyclization factors were measured to be several orders of magnitude greater than those predicted by the WLC model for DNA lengths below 100 base pairs (bp). This phenomenon implied an increase in dsDNA flexibility, possibly due to a flexible hinge in the form of kinks and bubbles that can form under strong bending 11 12 13 14 15 .…”

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confidence: 99%

Two conformational states in D-shaped DNA: Effects of local denaturation

Lee

Kim

et al. 2016

Sci Rep

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The bending of double-stranded(ds) DNA on the nano-meter scale plays a key role in many cellular processes such as nucleosome packing, transcription-control, and viral-genome packing. In our recent study, a nanometer-sized dsDNA bent into a D shape was formed by hybridizing a circular single-stranded(ss) DNA and a complementary linear ssDNA. Our fluorescence resonance energy transfer (FRET) measurement of D-DNA revealed two types of conformational states: a less-bent state and a kinked state, which can transform into each other. To understand the origin of the two deformed states of D-DNA, here we study the presence of open base-pairs in the ds portion by using the breathing-DNA model to simulate the system. We provide strong evidence that the two states are due to the emergence of local denaturation, i.e., a bubble in the middle and two forks at ends of the dsDNA portion. We also study the system analytically and find that the free-energy landscape is bistable with two minima representative of the two states. The kink and fork sizes estimated by the analytical calculation are also in excellent agreement with the results of the simulation. Thus, this combined experimental-simulation-analytical study corroborates that highly bent D-DNA reduces bending stress via local denaturation.

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“…A more likely explanation is that the CSO model fails to capture the salient physics at the short segment lengths and needs to be further elaborated to accurately describe the cyclization of such sequences. In support of the latter explanation, it was previously suggested that (especially for fragments shorter than 70 bp) there is a need to consider a kink-able WLC [ 22 , 51 ] and/or melt-able WLC [ 4 , 52 , 53 ] models. Future studies will be needed to evaluate the performance of such models in regards to a large collection of DNA fragments with experimentally measured J factors.…”

Section: Discussionmentioning

confidence: 98%

The role of structural parameters in DNA cyclization

Alexandrov¹,

Bishop²,

Rasmussen³

et al. 2016

BMC Bioinformatics

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BackgroundThe intrinsic bendability of DNA plays an important role with relevance for myriad of essential cellular mechanisms. The flexibility of a DNA fragment can be experimentally and computationally examined by its propensity for cyclization, quantified by the Jacobson-Stockmayer J factor. In this study, we use a well-established coarse-grained three-dimensional model of DNA and seven distinct sets of experimentally and computationally derived conformational parameters of the double helix to evaluate the role of structural parameters in calculating DNA cyclization.ResultsWe calculate the cyclization rates of 86 DNA sequences with previously measured J factors and lengths between 57 and 325 bp as well as of 20,000 randomly generated DNA sequences with lengths between 350 and 4000 bp. Our comparison with experimental data is complemented with analysis of simulated data.ConclusionsOur data demonstrate that all sets of parameters yield very similar results for longer DNA fragments, regardless of the nucleotide sequence, which are in agreement with experimental measurements. However, for DNA fragments shorter than 100 bp, all sets of parameters performed poorly yielding results with several orders of magnitude difference from the experimental measurements. Our data show that DNA cyclization rates calculated using conformational parameters based on nucleosome packaging data are most similar to the experimental measurements. Overall, our study provides a comprehensive large-scale assessment of the role of structural parameters in calculating DNA cyclization rates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-0897-9) contains supplementary material, which is available to authorized users.

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How a short double-stranded DNA bends

Cited by 13 publications

References 39 publications

Coarse-Grained Modelling of Extreme DNA Bending

Coarse-Grained Modelling of Extreme DNA Bending

Two conformational states in D-shaped DNA: Effects of local denaturation

The role of structural parameters in DNA cyclization

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