DNA overwinds when stretched

Gore, Jeff; Bryant, Zev; Nöllmann, Marcelo; Le, Mai U.; Cozzarelli, Nicholas R.; Bustamante, Carlos

doi:10.1038/nature04974

Cited by 372 publications

(500 citation statements)

References 27 publications

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“…It is worth noting that in the region near the initial B-DNA structure ( Ͼ 9.5 Å), for which DNA is still in the entropic regime (F Յ 10 pN), we were also able to calculate (see supporting information for details) a twist͞stretch coupling constant of Ϫ15 nm. This finding agrees, both in sign and absolute value, with recent single molecule experiments indicating that, near the B form of DNA, an increase in twist leads to an increase in extension (33,34).…”

Section: Equilibrium Calculations Free Energy and Equilibrium Forces supporting

confidence: 80%

“…The calculation of the free energy profile in the vicinity of B-DNA has additionally provided an equilibrium twist-elongation dependence (see supporting information) that enabled the calculation, in the low-twist limit, of a negative twist-stretch coupling constant of Ϫ15 nm, in accord with recent experiments (33,34).…”

Section: Concluding Discussionmentioning

confidence: 54%

“…This is not totally unexpected, given twist-stretch coupling in DNA (33,34,38,39), and is in accord with the fact that stretching longitudinally undertwisted DNA induces a flipping out of bases that can activate homologous pairing in physiological conditions (15).…”

Section: Concluding Discussionmentioning

confidence: 63%

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On structural transitions, thermodynamic equilibrium, and the phase diagram of DNA and RNA duplexes under torque and tension

Wereszczynski

Andricioaei

2006

Proc. Natl. Acad. Sci. U.S.A.

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A precise understanding of the flexibility of double stranded nucleic acids and the nature of their deformed conformations induced by external forces is important for a wide range of biological processes including transcriptional regulation, supercoil and catenane removal, and site-specific recombination. We present, at atomic resolution, a simulation of the dynamics involved in the transitions from B-DNA and A-RNA to Pauling (P) forms and to denatured states driven by application of external torque and tension. We then calculate the free energy profile along a B-to P-transition coordinate and from it, compute a reversible pathway, i.e., an isotherm of tension and torque pairs required to maintain P-DNA in equilibrium. The reversible isotherm maps correctly onto a phase diagram derived from single molecule experiments, and yields values of elongation, twist, and twist-stretch coupling in agreement with measured values. We also show that configurational entropy compensates significantly for the large electrostatic energy increase due to closer-packed P backbones. A similar set of simulations applied to RNA are used to predict a novel structure, P-RNA, with its associated free energy, equilibrium tension, torque and structural parameters, and to assign the location, on the phase-diagram,

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Section: Equilibrium Calculations Free Energy and Equilibrium Forces supporting

confidence: 80%

Section: Concluding Discussionmentioning

confidence: 54%

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On structural transitions, thermodynamic equilibrium, and the phase diagram of DNA and RNA duplexes under torque and tension

Wereszczynski

Andricioaei

2006

Proc. Natl. Acad. Sci. U.S.A.

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“…From well-defined oligomers of DNA, the stretch-torsion coupling can be obtained via magnetic tweezers and measuring the consequent over-or under-winding of the helix by tracking an attached rotor bead. In the work of Gore et al [7], a stretching elastic modulus is reported, which equates to an inter base-pair force constant of 3 N=m. Another example of a molecular sculpturing approach involves DNA oligomers capped with gold nanoparticles, which allow the end-to-end distance to be measured by small angle x-ray scattering [8].…”

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confidence: 99%

Direct Determination of the Base-Pair Force Constant of DNA from the Acoustic Phonon Dispersion of the Double Helix

et al. 2011

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Quantifying the molecular elasticity of DNA is fundamental to our understanding of its biological functions. Recently different groups, through experiments on tailored DNA samples and numerical models, have reported a range of stretching force constants (0.3 to 3 N=m). However, the most direct, microscopic measurement of DNA stiffness is obtained from the dispersion of its vibrations. A new neutron scattering spectrometer and aligned, wet spun samples have enabled such measurements, which provide the first data of collective excitations of DNA and yield a force constant of 83 N=m. Structural and dynamic order persists unchanged to within 15 K of the melting point of the sample, precluding the formation of bubbles. These findings are supported by large scale phonon and molecular dynamics calculations, which reconcile hard and soft force constants. DOI: 10.1103/PhysRevLett.107.088102 PACS numbers: 87.14.gk, 63.22.Àm, 78.70.Nx, 87.10.Tf DNA stores the genetic code of all living organisms. Its principle biological functions of DNA are therefore transcription and replication. These processes take place in cells where DNA undergoes protein-mediated, mechanical manipulation resulting in folding, coiling and denaturing of the DNA molecule. The elasticity of DNA also underpins cleavage by enzymes [1] and the formation of 'bubbles' of locally denatured zones along the helix [2,3]. Models describing biologically relevant processes depend on the mechanical properties of DNA expressed as parameters, such as the base-pair force constant, which is crucial in the process of denaturing of DNA [4,5]. All measurements of DNA elasticity are therefore important in understanding the biological function of DNA and here we focus on stretching elasticity and the underlying base-pair stacking interaction.Recently considerable progress has been made in measuring the flexibility of the DNA helix although one concern is the extent to which the experimental or theoretical approaches themselves influence the results [6]. From well-defined oligomers of DNA, the stretch-torsion coupling can be obtained via magnetic tweezers and measuring the consequent over-or under-winding of the helix by tracking an attached rotor bead. In the work of Gore et al.[7], a stretching elastic modulus is reported, which equates to an inter base-pair force constant of 3 N=m. Another example of a molecular sculpturing approach involves DNA oligomers capped with gold nanoparticles, which allow the end-to-end distance to be measured by small angle x-ray scattering [8]. This work reported corresponding values 10 times smaller: 0:3 N=m. Similarly, Wiggins et al.[9] extracted bending force constants from single DNA molecule conformations on a substrate. They too found that the corresponding force constants are much smaller on a local length scale than predicted by classical elasticity models. A more theoretical approach [10] uses the well-known melting temperatures of DNA to calculate the flexibility on a local length scale via the Peyrard-Bishop model [11], assuming ...

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“…Equation (10) does not predict the tiny anomalous overwinding under tension [15]. We believe this is a consequence of neglecting the bending modes, whose thermal fluctuation weakens the base's bonds.…”

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confidence: 98%

Thermomechanics of DNA: Theory of Thermal Stability under Load

Nisoli

Bishop

2011

Phys. Rev. Lett.

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A theory for thermomechanical behavior of homogeneous DNA at thermal equilibrium predicts critical temperatures for denaturation under torque and stretch, phase diagrams for stable B-DNA, supercoiling, optimally stable torque, and the overstretching transition as force-induced DNA melting. Agreement with available single molecule manipulation experiments is excellent.PACS numbers: 87.14.gk, 87.15.ad, 87.15.Zg,64.60.De DNA is a highly refined nanomechanical object. The interplay between strong covalent bonds of the backbone and weak hydrogen interactions between bases [1], the thermal bath in which it is immersed, and the proximity of physiological conditions to the denaturation temperature, make DNA highly and non-linearly responsive to mechanical and thermal changes, and render any solely mechanical approach inviable. This is critical for nanotechnology, where DNA is the basis for novel materials [2], but understanding double helix thermomechanics would also illuminate biology, where enzymes involved in replication and repair are viewed as molecular motors.In the past twenty years, direct single molecule manipulation [3,4] has revolutionized our understanding of key aspects of DNA, revealing new couplings and transitions between different structures, whose nature and forms, however, are still speculative. When a few micrometer long strand of DNA is stretched to a tension of the order of pico-Newtons (pNs) to avoid formation of plectonemes, sharp transitions are activated at positive and negative torques, while an overstretching transition is observed for DNA under tension of 60 pN at zero torque [5]. Tentative tension-torque phase diagrams for the stability of B-DNA, and various phenomenological theories, have been proposed to explain these effects. The robustness of the Peyrard-Bishop-Dauxois approach (PBD) [6][7][8] has been corroborated by Cocco and Barbi [9, 10]: they incorporated torque and successfully reproduced denaturation by unwinding. However, these recent studies do not include tension, do not explain denaturation at overwinding, and do not provide phase diagrams in the tension-torque plane. Also, although much simpler than the molecular structure they describe, their complexity still calls for numerical treatments, and cannot offer analytic equations to more easily guide experiments.We address these issues by modeling the steric dependence of the base bond and the effect of tension and torque in a way suitable for elimination of the angular degrees of freedom via integration of the partition function, and obtain an effective energy for a PBD model which incorporates temperature and external loads. We compute the phase diagram for B-DNA and the dependence of supercoiling on torque, tension and temperature at criticality. Finally, we propose simple algebraic formulae for the observables.In our model i labels nucleotides separated by a distance a along the DNA backbone (Fig. 1), x i is the length of the i th base's bond, ω i = (θ i+1 − θ i−1 )/2 − Ω is the angular shift between nucleotides along th...

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DNA overwinds when stretched

Cited by 372 publications

References 27 publications

On structural transitions, thermodynamic equilibrium, and the phase diagram of DNA and RNA duplexes under torque and tension

On structural transitions, thermodynamic equilibrium, and the phase diagram of DNA and RNA duplexes under torque and tension

Direct Determination of the Base-Pair Force Constant of DNA from the Acoustic Phonon Dispersion of the Double Helix

Thermomechanics of DNA: Theory of Thermal Stability under Load

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