Nucleic acid double helix - Knowledge (XXG)

821:. It has three significant degrees of freedom; bending, twisting, and compression, each of which cause certain limits on what is possible with DNA within a cell. Twisting-torsional stiffness is important for the circularisation of DNA and the orientation of DNA bound proteins relative to each other and bending-axial stiffness is important for DNA wrapping and circularisation and protein interactions. Compression-extension is relatively unimportant in the absence of high tension. 1814: 551: 749: 841: 312: 543: 527:-DNA), P-DNA, S-DNA, Z-DNA, etc. have been described so far. In fact, only the letters F, Q, U, V, and Y are now available to describe any new DNA structure that may appear in the future. However, most of these forms have been created synthetically and have not been observed in naturally occurring biological systems. There are also 764:. As the strands are not directly opposite each other, the grooves are unequally sized. One groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide. The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like 429:"Tilt" has often been used differently in the scientific literature, referring to the deviation of the first, inter-strand base-pair axis from perpendicularity to the helix axis. This corresponds to slide between a succession of base pairs, and in helix-based coordinates is properly termed "inclination". 971:

DNA in solution does not take a rigid structure but is continually changing conformation due to thermal vibration and collisions with water molecules, which makes classical measures of rigidity impossible to apply. Hence, the bending stiffness of DNA is measured by the persistence length, defined as:

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However, the discovery of topoisomerases took "the sting" out of the topological objection to the plectonaemic double helix. The more recent solution of the single crystal X-ray structure of the nucleosome core particle showed nearly 150 base pairs of the DNA (i.e., about 15 complete turns), with a

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Any change of T in a closed topological domain must be balanced by a change in W, and vice versa. This results in higher order structure of DNA. A circular DNA molecule with a writhe of 0 will be circular. If the twist of this molecule is subsequently increased or decreased by supercoiling then the

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Periodic fracture of the base-pair stack with a break occurring once per three bp (therefore one out of every three bp-bp steps) has been proposed as a regular structure which preserves planarity of the base-stacking and releases the appropriate amount of extension, with the term "Σ-DNA" introduced

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DNA circularization depends on both the axial (bending) stiffness and torsional (rotational) stiffness of the molecule. For a DNA molecule to successfully circularize it must be long enough to easily bend into the full circle and must have the correct number of bases so the ends are in the correct

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to directly image DNA molecules of various lengths. In an aqueous solution, the average persistence length has been found to be of around 50 nm (or 150 base pairs). More broadly, it has been observed to be between 45 and 60 nm or 132–176 base pairs (the diameter of DNA is 2 nm) This

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Bending flexibility of a polymer is conventionally quantified in terms of its persistence length, Lp, a length scale below which the polymer behaves more or less like a rigid rod. Specifically, Lp is defined as length of the polymer segment over which the time-averaged orientation of the polymer

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In considering supercoils formed by closed double-stranded molecules of DNA certain mathematical concepts, such as the linking number and the twist, are needed. The meaning of these for a closed ribbon is explained and also that of the writhing number of a closed curve. Some simple examples are

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The geometry of a base, or base pair step can be characterized by 6 coordinates: shift, slide, rise, tilt, roll, and twist. These values precisely define the location and orientation in space of every base or base pair in a nucleic acid molecule relative to its predecessor along the axis of the

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Preferred DNA bend direction is determined by the stability of stacking each base on top of the next. If unstable base stacking steps are always found on one side of the DNA helix then the DNA will preferentially bend away from that direction. As bend angle increases then steric hindrances and

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Proposed S-DNA structures include those which preserve base-pair stacking and hydrogen bonding (GC-rich), while releasing extension by tilting, as well as structures in which partial melting of the base-stack takes place, while base-base association is nonetheless overall preserved (AT-rich).

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in prokaryotes) which are topologically closed, or as very long molecules whose diffusion coefficients produce effectively topologically closed domains. Linear sections of DNA are also commonly bound to proteins or physical structures (such as membranes) to form closed topological loops.

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The B form of the DNA helix twists 360° per 10.4-10.5 bp in the absence of torsional strain. But many molecular biological processes can induce torsional strain. A DNA segment with excess or insufficient helical twisting is referred to, respectively, as positively or negatively

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Rise and twist determine the handedness and pitch of the helix. The other coordinates, by contrast, can be zero. Slide and shift are typically small in B-DNA, but are substantial in A- and Z-DNA. Roll and tilt make successive base pairs less parallel, and are typically small.

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rotation to allow bonding to occur. The optimum length for circularization of DNA is around 400 base pairs (136 nm), with an integral number of turns of the DNA helix, i.e., multiples of 10.4 base pairs. Having a non integral number of turns presents a significant

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reasons, more compact relaxed states are thermally accessible than stretched out states, and so DNA molecules are almost universally found in a tangled relaxed layouts. For this reason, one molecule of DNA will stretch under a force, straightening it out. Using

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The intrinsically bent structure is induced by the 'propeller twist' of base pairs relative to each other allowing unusual bifurcated Hydrogen-bonds between base steps. At higher temperatures this structure is denatured, and so the intrinsic bend is lost.

1927:. These enzymes are dedicated to un-knotting circular DNA by cleaving one or both strands so that another double or single stranded segment can pass through. This un-knotting is required for the replication of circular DNA and various types of 1872:= twist - total number of turns in the double stranded DNA helix. This will normally tend to approach the number of turns that a topologically open double stranded DNA helix makes free in solution: number of bases/10.5, assuming there are no 1787:. These structures have not yet been definitively characterised due to the difficulty of carrying out atomic-resolution imaging in solution while under applied force although many computer simulation studies have been made (for example,). 480:

A-DNA and Z-DNA differ significantly in their geometry and dimensions to B-DNA, although still form helical structures. It was long thought that the A form only occurs in dehydrated samples of DNA in the laboratory, such as those used in

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structure that is in all essential respects the same as the Watson–Crick model. This dealt a death blow to the idea that other forms of DNA, particularly double helical DNA, exist as anything other than local or transient structures.

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binding to form a double helix. Melting is the process by which the interactions between the strands of the double helix are broken, separating the two nucleic acid strands. These bonds are weak, easily separated by gentle heating,

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For many years, the origin of residual supercoiling in eukaryotic genomes remained unclear. This topological puzzle was referred to by some as the "linking number paradox". However, when experimentally determined structures of the

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as a mnemonic, with the three right-facing points of the Sigma character serving as a reminder of the three grouped base pairs. The Σ form has been shown to have a sequence preference for GNC motifs which are believed under the

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by which genetic information is stored and copied in living organisms and is widely considered one of the most important scientific discoveries of the 20th century. Crick, Wilkins, and Watson each received one-third of the 1962

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The bending of short circularized DNA segments is non-uniform. Rather, for circularized DNA segments less than the persistence length, DNA bending is localised to 1-2 kinks that form preferentially in AT-rich segments. If a

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All DNA which bends anisotropically has, on average, a longer persistence length and greater axial stiffness. This increased rigidity is required to prevent random bending which would make the molecule act isotropically.

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The persistence length of a section of DNA is somewhat dependent on its sequence, and this can cause significant variation. The variation is largely due to base stacking energies and the residues which extend into the

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for regulatory purposes may adopt the Z geometry, in which the strands turn about the helical axis the opposite way to A-DNA and B-DNA. There is also evidence of protein-DNA complexes forming Z-DNA structures.

1923:. This means the single strands cannot be separated any process that does not involve breaking a strand (such as heating). The task of un-knotting topologically linked strands of DNA falls to enzymes termed 768:

that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell

2830: 140:. In B-DNA the major groove is wider than the minor groove. Given the difference in widths of the major groove and minor groove, many proteins which bind to B-DNA do so through the wider major groove. 3988:

Konrad MW, Bolonick JW (1996). "Molecular dynamics simulation of DNA stretching is consistent with the tension observed for extension and strand separation and predicts a novel ladder structure".

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Twin helical strands form the DNA backbone. Another double helix may be found by tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a

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residues will be preferentially be found in the minor grooves on the inside of bends. This effect is particularly seen in DNA-protein binding where tight DNA bending is induced, such as in

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Olson WK, Bansal M, Burley SK, Dickerson RE, Gerstein M, Harvey SC, et al. (October 2001). "A standard reference frame for the description of nucleic acid base-pair geometry".

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Evidence from mechanical stretching of DNA in the absence of imposed torque points to a transition or transitions leading to further structures which are generally referred to as

132:, the most common double helical structure found in nature, the double helix is right-handed with about 10–10.5 base pairs per turn. The double helix structure of DNA contains a 1191:

bending. This is, again, due to the properties of the bases which make up the DNA sequence - a random sequence will have no preferred bend direction, i.e., isotropic bending.

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Longer stretches of DNA are entropically elastic under tension. When DNA is in solution, it undergoes continuous structural variations due to the energy available in the

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Davey CA, Sargent DF, Luger K, Maeder AW, Richmond TJ (June 2002). "Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution".

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was one of the first to propose the importance of linking numbers when considering DNA supercoils. In a paper published in 1976, Crick outlined the problem as follows:

4351: 1176:) forces. For DNA segments less than the persistence length, the bending force is approximately constant and behaviour deviates from the worm-like chain predictions. 1961: 1866:= linking number - the number of times one DNA strand wraps around the other. It is an integer for a closed loop and constant for a closed topological domain. 773:, but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form. 4093:"DNA partitions into triplets under tension in the presence of organic cations, with sequence evolutionary age predicting the stability of the triplet phase" 1715:

for circularization, for example a 10.4 x 30 = 312 base pair molecule will circularize hundreds of times faster than 10.4 x 30.5 ≈ 317 base pair molecule.

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of sequence. The double helix makes one complete turn about its axis every 10.4–10.5 base pairs in solution. This frequency of twist (termed the helical

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Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ (September 1997). "Crystal structure of the nucleosome core particle at 2.8 A resolution".

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can vary significantly due to variations in temperature, aqueous solution conditions and DNA length. This makes DNA a moderately stiff molecule.

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Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, et al. (October 1980). "Crystal structure analysis of a complete turn of B-DNA".

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Vargason JM, Eichman BF, Ho PS (September 2000). "The extended and eccentric E-DNA structure induced by cytosine methylation or bromination".

2085: 221: 3657:"The persistence length of DNA is reached from the persistence length of its null isomer through an internal electrostatic stretching force" 3191: 4449: 4344: 1981: 1179:

This effect results in unusual ease in circularising small DNA molecules and a higher probability of finding highly bent sections of DNA.

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with the bases splaying outwards and the phosphates moving to the middle. This proposed structure for overstretched DNA has been called

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of the solvent. This is due to the thermal vibration of the molecule combined with continual collisions with water molecules. For

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Supercoiled structure of circular DNA molecules with low writhe. The helical aspect of the DNA duplex is omitted for clarity.

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Protozanova E, Yakovchuk P, Frank-Kamenetskii MD (September 2004). "Stacked-unstacked equilibrium at the nick site of DNA".

365:: displacement along an axis in the base-pair plane perpendicular to the first, directed from the minor to the major groove. 1737: 797:. However, the models were set aside in favor of the double-helical model due to subsequent experimental advances such as 31: 4401: 4391: 1873: 149: 1233:

rich sections which keep the A and T residues in phase with the minor groove on one side of the molecule. For example:

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For each base pair, considered relative to its predecessor, there are the following base pair geometries to consider:

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Watson JD, Crick FH (April 1953). "Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid".

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is typically negatively supercoiled, which facilitates the unwinding (melting) of the double-helix required for RNA

4386: 295:, which can chemically cleave the phosphate backbone of one of the strands so that it can swivel around the other. 870: 855: 4376: 3882:"Identifying Physical Causes of Apparent Enhanced Cyclization of Short DNA Molecules with a Coarse-Grained Model" 284: 2030:

Cobb M, Comfort N (April 2023). "What Rosalind Franklin truly contributed to the discovery of DNA's structure".

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writhe will be appropriately altered, making the molecule undergo plectonemic or toroidal superhelical coiling.

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Chargaff E (June 1950). "Chemical specificity of nucleic acids and mechanism of their enzymatic degradation".

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When the ends of a piece of double stranded helical DNA are joined so that it forms a circle the strands are

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helix. Together, they characterize the helical structure of the molecule. In regions of DNA or RNA where the

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Shimada J, Yamakawa H (1984). "Ring-Closure Probabilities for Twisted Wormlike Chains. Application to DNA".

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DNA molecules with exceptional bending preference can become intrinsically bent. This was first observed in

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Bosaeus N, Reymer A, Beke-Somfai T, Brown T, Takahashi M, Wittung-Stafshede P, et al. (January 2017).

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Roe DR, Chaka AM (November 2009). "Structural basis of pathway-dependent force profiles in stretched DNA".

4421: 4411: 4360: 4193:"A topological approach to nucleosome structure and dynamics: the linking number paradox and other issues" 2923:

Lu XJ, Olson WK (January 1999). "Resolving the discrepancies among nucleic acid conformational analyses".

474: 809:. Also, the non-double-helical models are not currently accepted by the mainstream scientific community. 4429: 1928: 798: 1839:

Within the cell most DNA is topologically restricted. DNA is typically found in closed loops (such as

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ability to roll the residues relative to each other also play a role, especially in the minor groove.

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Wilkins MH, Stokes AR, Wilson HR (April 1953). "Molecular structure of deoxypentose nucleic acids".

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Chargaff E (July 1951). "Some recent studies on the composition and structure of nucleic acids".

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Elson D, Chargaff E (April 1952). "On the desoxyribonucleic acid content of sea urchin gametes".

2400: 2231: 1966: 1150: 830: 371:: displacement along an axis in the plane of the base pair directed from one strand to the other. 47:

regions of nucleic acid molecules will bind and form a double helical structure held together by

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The realization that the structure of DNA is that of a double-helix elucidated the mechanism of

473:) depends largely on stacking forces that each base exerts on its neighbours in the chain. The 4396: 4368: 4316: 4273: 4230: 4173: 4114: 4073: 4032: 3962: 3913: 3824: 3789: 3740: 3686: 3634: 3519: 3474: 3435: 3368: 3307: 3284: 3249: 3172: 3110: 3061: 3018: 2975: 2940: 2905: 2760: 2687: 2620: 2585: 2525: 2484: 2435: 2392: 2308: 2223: 2180: 2142: 2081: 2055: 1712: 173: 103:, while the term "double helix" entered popular culture with the 1968 publication of Watson's 88: 56: 4556: 4515: 4308: 4265: 4220: 4212: 4163: 4153: 4104: 4063: 4024: 3997: 3952: 3903: 3893: 3859: 3816: 3779: 3771: 3730: 3720: 3709:"Atomic Force Microscopy Investigation of the Interactions between the MCM Helicase and DNA" 3676: 3668: 3624: 3614: 3511: 3466: 3427: 3358: 3348: 3276: 3241: 3162: 3152: 3100: 3053: 3010: 2967: 2932: 2895: 2887: 2750: 2740: 2677: 2667: 2612: 2575: 2515: 2474: 2427: 2384: 2347: 2298: 2266: 2215: 2172: 2132: 2122: 2047: 1877: 1769: 1746: 324:

structure is disrupted, the change in these values can be used to describe such disruption.

250:, or mechanical force. Melting occurs preferentially at certain points in the nucleic acid. 160: 105: 1813: 3546: 1757: 1750: 1165: 1161: 1154: 818: 786: 482: 280:

at the start of many genes to assist RNA polymerase in melting the DNA for transcription.

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Rich A, Nordheim A, Wang AH (1984). "The chemistry and biology of left-handed Z-DNA".

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of the bases determines the direction of the helical curve for a given conformation.

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Stokes TD (May 1982). "The double helix and the warped zipper--an exemplary tale".

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rich regions. Some base steps (pairs) are also susceptible to DNA melting, such as

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Neidle S, Sanderson M (2022). "DNA structure as observed in fibres and crystals".

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Richmond TJ, Davey CA (May 2003). "The structure of DNA in the nucleosome core".

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were briefly considered in the late 1970s as a potential solution to problems in

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unwind the strands to facilitate the advance of sequence-reading enzymes such as

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