In molecular biology, the double helix is the structure formed by double-stranded molecules of nucleic acids such as DNA. The double-helical structure of a nucleic acid complex arises as a consequence of its secondary structure, and is a fundamental component in determining its tertiary structure.
The DNA double-helix biopolymer of nucleic acids is held together by nucleotides which base pair together. In B-DNA, 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 major groove and minor groove. 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.
The double helix structure of DNA was first proposed by James Watson and Francis Crick, based on the work of Rosalind Franklin, Raymond Gosling, Maurice Wilkins, and others. The term "double helix" entered popular culture with the 1968 publication of Watson's The Double Helix: A Personal Account of the Discovery of the Structure of DNA.
History
The double-helix model of DNA structure was first published in the journal Nature by James Watson and Francis Crick in 1953, (X,Y,Z coordinates in 1954) based on the work of Rosalind Franklin and her student Raymond Gosling, who took the crucial X-ray diffraction image of DNA labeled as "Photo 51", and Maurice Wilkins, Alexander Stokes, and Herbert Wilson, and base-pairing chemical and biochemical information by Erwin Chargaff. Before this, Linus Pauling—who had already accurately characterised the conformation of protein secondary structure motifs—and his collaborator Robert Corey had incorrectly proposed that DNA would adopt a triple-stranded conformation.
The realization that the structure of DNA is double-helix elucidated the mechanism of base pairing 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 Nobel Prize in Physiology or Medicine for their contributions to the discovery.
Nucleic acid hybridization
Hybridization is the process of complementary base pairs 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, enzymes, or mechanical force. Melting occurs preferentially at certain points in the nucleic acid. T and A rich regions are more easily melted than C and G rich regions. Some base steps (pairs) are also susceptible to DNA melting, such as T A and T G. These mechanical features are reflected by the use of sequences such as TATA at the start of many genes to assist RNA polymerase in melting the DNA for transcription.
Strand separation by gentle heating, as used in polymerase chain reaction (PCR), is simple, provided the molecules have fewer than about 10,000 base pairs (10 kilobase pairs, or 10 kbp). The intertwining of the DNA strands makes long segments difficult to separate. The cell avoids this problem by allowing its DNA-melting enzymes (helicases) to work concurrently with topoisomerases, which can chemically cleave the phosphate backbone of one of the strands so that it can swivel around the other. Helicases unwind the strands to facilitate the advance of sequence-reading enzymes such as DNA polymerase.
Base-pair geometry
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 helix. Together, they characterize the helical structure of the molecule. In regions of DNA or RNA where the normal structure is disrupted, the change in these values can be used to describe such disruption.
For each base pair, considered relative to its predecessor, there are the following base pair geometries to consider: Shear Stretch Stagger Buckle Propeller: rotation of one base with respect to the other in the same base pair. Opening Shift: displacement along an axis in the base-pair plane perpendicular to the first, directed from the minor to the major groove. Slide: displacement along an axis in the plane of the base pair directed from one strand to the other. Rise: displacement along the helix axis. Tilt: rotation around the shift axis. Roll: rotation around the slide axis. Twist: rotation around the rise axis. X-displacement Y-displacement Inclination Tip Pitch: the height per complete turn of the helix.
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.
"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".
Helix geometries
At least three DNA conformations are believed to be found in nature, A-DNA, B-DNA, and Z-DNA. The B form described by James Watson and Francis Crick is believed to predominate in cells. It is 23.7 Å wide and extends 34 Å per 10 bp of sequence. The double helix has a right-hand twist that makes one complete turn about its axis every 10.4–10.5 base pairs in solution. This frequency of twist (termed the helical pitch) depends largely on stacking forces that each base exerts on its neighbours in the chain.
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 crystallographic experiments, and in hybrid pairings of DNA and RNA strands, but DNA dehydration does occur in vivo, and A-DNA is now known to have biological functions. Segments of DNA that cells have methylated 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.
Other conformations are possible; A-DNA, B-DNA, C-DNA, E-DNA, L-DNA (the enantiomer of D-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 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 triple-stranded DNA forms and quadruplex forms such as the G-quadruplex and the i-motif.
+ Structural features of the three major forms of DNAGeometry attributeA-DNAB-DNAZ-DNAHelix sense right-handed right-handed left-handedRepeating unit 1 bp 1 bp 2 bpRotation/bp 32.7° 34.3° 60°/2bp/turn 11 10.5 12Inclination of bp to axis +19° −1.2° −9°Rise/bp along axis 2.3 Å (0.23 nm) 3.32 Å (0.332 nm) 3.8 Å (0.38 nm)Pitch/turn of helix 28.2 Å (2.82 nm) 33.2 Å (3.32 nm) 45.6 Å (4.56 nm)Mean propeller twist +18° +16° 0°Glycosyl angle anti anti C: anti, G: synSugar pucker C3'-endo C2'-endo C: C2'-endo,G: C2'-exoDiameter 23 Å (2.3 nm) 20 Å (2.0 nm) 18 Å (1.8 nm)
Grooves
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 binding site. 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 transcription factors 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 (see below), 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.
Non-double helical forms Alternative non-helical models were briefly considered in the late 1970s as a potential solution to problems in DNA replication in plasmids and chromatin. However, the models were set aside in favor of the double-helical model due to subsequent experimental advances such as X-ray crystallography of DNA duplexes and later the nucleosome core particle, and the discovery of topoisomerases. Also, the non-double-helical models are not currently accepted by the mainstream scientific community.
Bending DNA is a relatively rigid polymer, typically modelled as a worm-like chain. 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.
Persistence length, axial stiffness
+ Example sequences and their persistence lengths (B DNA) Sequence Persistence length/ base pairs Random 154±10 (CA)repeat 133±10 (CAG)repeat 124±10 (TATA)repeat 137±10
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:
This value may be directly measured using an atomic force microscope 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 can vary significantly due to variations in temperature, aqueous solution conditions and DNA length. This makes DNA a moderately stiff molecule.
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 minor and major grooves.
Models for DNA bending + Stacking stability of base steps (B DNA) Step Stacking ΔG /kcal mol−1 T A -0.19 T G or C A -0.55 C G -0.91 A G or C T -1.06 A A or T T -1.11 A T -1.34 G A or T C -1.43 C C or G G -1.44 A C or G T -1.81 G C -2.17 At length-scales larger than the persistence length, the entropic flexibility of DNA is remarkably consistent with standard polymer physics models, such as the Kratky-Porod worm-like chain model. Consistent with the worm-like chain model is the observation that bending DNA is also described by Hooke's law at very small (sub-piconewton) forces. For DNA segments less than the persistence length, the bending force is approximately constant and behaviour deviates from the worm-like chain predictions.
This effect results in unusual ease in circularising small DNA molecules and a higher probability of finding highly bent sections of DNA.
Bending preference