DNA helices: basic concepts, structure, functions and genetics

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DNA helices: basic concepts, structure, functions and genetics
DNA helices: basic concepts, structure, functions and genetics
Anonim

The term "DNA helix" has a complex history and nature. By it, as a rule, is meant the model introduced by James Watson. The DNA double helix is held together with nucleotides that form a pair. In B-DNA, the most common helical structure found in nature, the double helix is right-handed with 10-10.5 base pairs per turn. The double helix structure of DNA contains a major groove and a minor groove. In B-DNA, the major groove is wider than the minor groove. Given the difference in width between the major and minor grooves, many proteins that bind to B-DNA do so through the wider major groove.

DNA helix from below
DNA helix from below

Discovery history

The structural model of the DNA double helix was first published in Nature by James Watson and Francis Crick in 1953 (X, Y, Z coordinates in 1954) based on a critical x-ray diffraction image of DNA labeled Photo 51, from Rosalind Franklin's 1952 work, followed by a clearer image of her takenRaymond Gosling, Maurice Wilkins, Alexander Stokes and Herbert Wilson. The preliminary model was three-stranded DNA.

The realization that the open structure is a double helix explains the mechanism by which two strands of DNA join into a helix, by which genetic information is stored and copied in living organisms. This discovery is considered one of the most important scientific insights of the twentieth century. Crick, Wilkins, and Watson each received one-third of the 1962 Nobel Prize in Physiology or Medicine for their contributions to the discovery. Franklin, whose breakthrough X-ray diffraction data was used to formulate the DNA helix, died in 1958 and was therefore ineligible for a Nobel Prize nomination.

Value for hybridization

Hybridization is the process of connecting base pairs that bind to form a double helix. Melting is the process by which interactions between double helix strands are disrupted, separating two lines of nucleic acids. These bonds are weak, easily separated by mild heat, enzymes, or mechanical force. Melting occurs predominantly at certain points in the nucleic acid. Regions of the DNA helix labeled T and A are more easily melted than regions C and G. Some base stages (pairs) are also susceptible to DNA melting, such as TA and TG. These mechanical traits are mirrored by sequences such as TATA at the beginning of many genes to help RNA polymerase melt the DNA for transcription.

Heating

Process separationstrands by shallow heating, as used in the polymerase chain reaction (PCR), is simple, provided the molecules are approximately 10,000 base pairs (10 kilobase pairs or 10 kbp). The intertwining of DNA strands makes it difficult to separate long segments. The cell avoids this problem by allowing its DNA melting enzymes (helicases) to work simultaneously with topoisomerases, which can chemically cleave the phosphate backbone of one of the strands so that it can turn around the other. Helicases unwind the strands to facilitate the passage of sequence-reading enzymes such as DNA polymerase. The DNA double helix is formed by the bonds of these strands.

Spiral on a blue background
Spiral on a blue background

Spiral geometry

The geometric component of the DNA structure can be characterized by 6 coordinates: shear, slide, rise, tilt, twist and turn. These values precisely determine the location and orientation in space of each pair of DNA strands. In regions of DNA or RNA where the normal structure is disrupted, a change in these values can be used to describe such a disruption.

Rise and turn are determined by the shape of the spiral. Other coordinates, on the contrary, can be equal to zero.

Note that "skew" is often used in various ways in the scientific literature, referring to the deviation of the first axis of the interstrand base from being perpendicular to the axis of the helix. This corresponds to sliding between the base sequence of the DNA double helix, and in geometric coordinates is correctly called"tilt".

Geometric differences in spirals

At least three DNA conformations are thought to occur naturally: A-DNA, B-DNA and Z-DNA. Form B, as described by James Watson and Francis Crick, is thought to be predominant in cells. It is 23.7 Å wide and lengthens 34 Å by 10 bp. sequences. The DNA double helix is formed by the bonds of two lines of ribonucleic acid, which make one complete revolution around its axis every 10.4-10.5 base pairs in solution. This twist frequency (called the helical pitch) depends largely on the stacking forces each base exerts on its neighbors in the chain. The absolute configuration of the bases determines the direction of the helical curve for a given conformation.

Differences and Functions

A-DNA and Z-DNA are significantly different in their geometry and size compared to B-DNA, although they still form helical structures. It has long been thought that the A form occurs only in dehydrated DNA samples in the laboratory used in crystallographic experiments and in hybrid DNA-RNA strand pairings, but DNA dehydration does occur in vivo, and A-DNA now has biological functions known to us. DNA segments whose cells have been methylated for regulatory purposes may adopt a Z geometry in which the strands rotate about the helical axis in the opposite manner to A-DNA and B-DNA. There is also evidence of protein-DNA complexes forming Z-DNA structures. The length of the DNA helix does not change in any way depending ontype.

3D model of DNA
3D model of DNA

Problems with names

In fact, only the letters F, Q, U, V, and Y are now available to name the different types of DNA that may be discovered in the future. However, most of these forms were created synthetically and have not been observed in natural biological systems. There are also three-stranded (3 strands of DNA) and quadrupole forms, such as the G-quadruplex.

Connection of threads

DNA double helix is formed by the bonds of helical strands. Since the threads are not directly opposite each other, the grooves between them are of uneven size. One groove, the main one, has a width of 22 Å, and the other, a small one, reaches a length of 12 Å. The narrowness of the secondary groove means that the edges of the bases are more accessible in the main groove. As a result, proteins such as transcription factors that can bind to specific sequences in the DNA double helix typically make contact with the sides of bases that are open in the main groove. This situation changes in unusual DNA conformations within the cell, but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA was twisted back into its normal B shape.

Creating a model

In the late 1970s, alternative non-helical models were briefly considered as a potential solution to the problems of DNA replication in plasmids and chromatin. However, they were abandoned in favor of the double coil model of DNA due to subsequent experimental advances such as X-raycrystallography of DNA duplexes. Also, non-double helix models are not currently accepted by the mainstream scientific community.

Single-stranded nucleic acids (ssDNA) do not take a helical shape and are described by models such as random coil or worm-like chain.

DNA is a relatively rigid polymer, typically modeled as a worm-like chain. Model stiffness is important for DNA circularization and the orientation of its associated proteins relative to each other, while hysteretic axial stiffness is important for DNA wrapping and protein circulation and interaction. Compression-elongation is relatively unimportant in the absence of high voltage.

Chemistry and genetics

DNA in solution does not take on a rigid structure, but constantly changes conformation due to thermal vibration and collision with water molecules, which makes it impossible to apply classical stiffness measures. Therefore, the flexural stiffness of DNA is measured by the persistence length, defined as "the length of DNA over which the time-averaged orientation of the polymer becomes coefficient uncorrelated."

This value can be accurately measured using an atomic force microscope to directly image DNA molecules of various lengths. In aqueous solution, the average constant length is 46-50 nm or 140-150 base pairs (DNA 2 nm), although this can vary considerably. This makes DNA a moderately rigid molecule.

The duration of the continuation of a DNA segment is highly dependent on its sequence, and this can lead to significantchanges. The latter are mostly due to stacking energy and fragments that propagate into minor and major grooves.

Physical properties and curves

The entropic flexibility of DNA is remarkably consistent with standard models of polymer physics, such as the Kratky-Porod model of the chainworm. Consistent with the worm-like model is the observation that bending DNA is also described by Hooke's law at very small (subpiconeontonic) forces. However, for segments of DNA smaller in duration and persistence, the bending force is approximately constant and the behavior deviates from predictions, in contrast to the already mentioned worm-like models.

This effect results in an unusual ease in circularizing small DNA molecules and a higher probability of finding highly curved DNA regions.

DNA molecules often have a preferred direction for bending, i.e. anisotropic bending. This, again, is due to the properties of the bases that make up the DNA sequences, and it is they that connect two strands of DNA into a helix. In some cases, sequences do not have the proverbial twists.

Computer model of DNA
Computer model of DNA

DNA double helix structure

The preferred direction of DNA bending is determined by the stacking stability of each base on top of the next. If unstable base stacking steps are always on one side of the DNA helix, then the DNA will preferentially fold away from that direction. Connecting two strands of DNA into a helixcarried out by molecules that depend on this direction. As the bending angle increases, they play the role of steric hindrances, showing the ability to roll the residues in relation to each other, especially in the small groove. Deposits A and T will preferably occur in small grooves within the bends. This effect is especially evident in DNA-protein binding when DNA rigid bending is induced, for example in nucleosome particles.

DNA molecules with exceptional bending can become bendy. This was first discovered in DNA from trypanosomatid kinetoplast. Typical sequences that cause this include 4-6 T and A stretches separated by G and C, which contain A and T residues in a minor groove phase on the same side of the molecule.

The internal bent structure is induced by the "screw-turning" of the base pairs relative to each other, which allows the creation of unusual bifurcated hydrogen bonds between the base stages. At higher temperatures, this structure is denatured and therefore the intrinsic curvature is lost.

All DNA that bends anisotropically has, on average, a longer thrust and greater axial stiffness. This increased stiffness is necessary to prevent accidental bending that would cause the molecule to act isotropically.

DNA ringing depends on both axial (flexural) rigidity and torsional (rotational) rigidity of the molecule. For a DNA molecule to circulate successfully, it must be long enough to bend easily into a full circle and have the correct number of bases tothe ends were in the correct rotation in order to ensure the possibility of gluing the spirals. The optimal length for circulating DNA is about 400 base pairs (136 nm). The presence of an odd number of turns is a significant energy barrier to circuits, for example, a 10.4 x 30=312 pair molecule will circulate hundreds of times faster than a 10.4 x 30.5 ≈ 317 molecule.

A model of DNA in the haze
A model of DNA in the haze

Elasticity

Longer stretches of DNA are entropically elastic when stretched. When DNA is in solution, it undergoes continuous structural changes due to the energy available in the thermal solvent bath. This is due to the thermal vibrations of the DNA molecule, combined with constant collisions with water molecules. For entropy reasons, more compact relaxed states are thermally more accessible than stretched states, and so DNA molecules are almost ubiquitous in intricate "relaxed" molecular models. For this reason, one DNA molecule will stretch under the force, straightening it. Using optical tweezers, the entropy stretching behavior of DNA has been studied and analyzed from the perspective of polymer physics, and it has been found that DNA behaves basically like a Kratky-Porod worm-like chain model on physiologically available energy scales.

With enough tension and positive torque, the DNA is thought to undergo a phase transition, with the backbones moving outwards and the phosphates moving intomiddle. This proposed structure for overstretched DNA was named P-form DNA after Linus Pauling, who originally envisioned it as a possible DNA structure.

Evidence for mechanical stretching of DNA in the absence of imposed torque points to a transition or transitions leading to further structures commonly referred to as S-shapes. These structures have not yet been definitively characterized due to the difficulty of performing resolution imaging of an atomic resonator in solution with force applied, although many computer simulation studies have been made. Suggested S-DNA structures include those that retain the base pair fold and hydrogen bond (enriched in GC).

DNA helix as it is
DNA helix as it is

Sigmoid model

Periodic fracture of the base-pair stack with a break has been proposed as a regular structure that retains the regularity of the base-stack and releases an appropriate amount of expansion, with the term "Σ-DNA" being introduced as a mnemonic in which the three right-hand dots of the "Sigma" symbol serve a reminder of three clustered base pairs. The form Σ has been shown to have a sequence preference for GNC motifs, which the GNC_h-hypothesis believes to have evolutionary significance.

Melting, heating and unwinding the spiral

Form B of the DNA helix twists 360° for 10.4-10.5 bp. in the absence of torsional deformation. But many molecular biological processes can induce torsional stress. A segment of DNA with an excess orundercoiling is mentioned in both positive and negative contexts, respectively. DNA in vivo is usually negatively coiled (i.e., has curls that are twisted in the opposite direction), which facilitates the unwinding (melting) of the double helix, which is sorely needed for RNA transcription.

Inside the cell, most DNA is topologically limited. DNA is usually found in closed loops (such as plasmids in prokaryotes) which are topologically closed or very long molecules whose diffusion coefficients effectively produce topologically closed regions. Linear stretches of DNA are also commonly associated with proteins or physical structures (such as membranes) to form closed topological loops.

Lots of strands of DNA
Lots of strands of DNA

Any change in the T parameter in a closed topological region must be balanced by a change in the W parameter, and vice versa. This results in a higher helix structure of DNA molecules. An ordinary DNA molecule with root 0 would be circular in its classification. If the twist of this molecule is subsequently increased or decreased by superconforming, then the roots will be altered accordingly, causing the molecule to undergo plectnonemic or toroidal superhelic winding.

When the ends of a section of the DNA double helix are connected so that it forms a circle, the strands are topologically tied. This means that individual threads cannot be separated from any process that is not associated with a thread break.(e.g. heating). The task of untying the topologically linked strands of DNA falls to enzymes called topoisomerases.

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