Watson and Crick DNA Model DNA stands for Deoxyribonucleic acid which is a molecule that contains the instructions an organism needs to

develop, live and reproduce. It is a type of nucleic acid and is one of the four major types of macromolecules that are known to be essential for

all forms of life.

DNA Model The three-dimensional structure of DNA, first proposed by James D. Watson and Francis H. C. Crick in 1953, consists

of two long helical strands that are coiled around a common axis to form a double helix. Each DNA molecule is comprised of two biopolymer strands coiling around each other. Each strand has a 5′end (with a phosphate group) and a 3′end (with a hydroxyl group). The strands are antiparallel, meaning that one strand runs in a 5′to 3′direction, while the other strand runs in a 3′to

5′direction. The diameter of the double helix is 2nm and the double helical structure repeats at an interval of 3.4nm which

corresponds to ten base pairs. The two strands are held together by hydrogen bonds and are complementary to each other. The two DNA strands are called polynucleotides, as they are made of simpler monomer units called nucleotides.

Basically, the DNA is composed of deoxyribonucleotides. The deoxyribonucleotides are linked together by 3′- 5′phosphodiester bonds. The nitrogenous bases that compose the deoxyribonucleotides include adenine, cytosine, thymine, and guanine. The structure of DNA -DNA is a double helix structure because it looks like a twisted ladder. The sides of the ladder are made of alternating sugar (deoxyribose) and phosphate molecules while the steps of the

ladder are made up of a pair of nitrogen bases. As a result of the double helical nature of DNA, the molecule has two asymmetric grooves. One groove is smaller

than the other. This asymmetry is a result of the geometrical configuration of the bonds between the phosphate, sugar, and base

groups that forces the base groups to attach at 120-degree angles instead of 180 degrees. The larger groove is called the major groove, occurs when the backbones are far apart; while the smaller one is

called the minor groove, and occurs when they are close together. Since the major and minor grooves expose the edges of the bases, the grooves can be used to tell the base

sequence of a specific DNA molecule. The possibility for such recognition is critical since proteins must be able to recognize specific DNA sequences on

which to bind in order for the proper functions of the body and cell to be carried out.

The Nitrogen Bases or Nucleotides DNA strands are composed of monomers called nucleotides. These monomers are often referred to as bases because they contain cyclic organic bases. Four different nucleotides, abbreviated A, T, C, and G, (adenine, thymine, cytosine, and guanine) are joined to form

a DNA strand, with the base parts projecting inward from the backbone of the strand. Two strands bind together via the bases and twist to form a double helix. The nitrogen bases have a specific pairing pattern. This pairing pattern occurs because the amount of adenine

equals the amount of thymine; the amount of guanine equals the amount of cytosine. The pairs are held together by hydrogen bonds.

Each DNA double helix thus has a simple construction: wherever one strand has an A, the other strand has a T, and each C is matched with a G.

The complementary of the strands are due to the nature of the nitrogenous bases. The base adenine always interacts with thymine (A-T) on the opposite strand via two hydrogen bonds and cytosine always interacts with guanine (C-G) via three hydrogen bonds on the opposite strand.

The shape of the helix is stabilized by hydrogen bonding and hydrophobic interactions between bases.

Deoxyribose Sugar Deoxyribose, also known as D-Deoxyribose and 2-deoxyribose, is a pentose sugar (monosaccharide containing five

carbon atoms) that is a key component of the nucleic acid deoxyribonucleic acid (DNA). It is derived from the pentose sugar ribose. Deoxyribose has the chemical formula C5H10O4. Deoxyribose is the sugar component of DNA, just as ribose serves that role in RNA (ribonucleic acid). Alternating with phosphate bases, deoxyribose forms the backbone of the DNA, binding to the nitrogenous

bases adenine, thymine, guanine, and cytosine. As a component of DNA, which represents the genetic information in all living cells, deoxyribose is critical to life.

This ubiquitous sugar reflects a commonality among all living organisms.

The Phosphate Group (Phosphate Backbone) The sugar-phosphate backbone forms the structural framework of nucleic acids, including DNA. This backbone is composed of alternating sugar and phosphate groups and defines directionality of the molecule. DNA are composed of nucleotides that are linked to one another in a chain by chemical bonds, called ester bonds,

between the sugar base of one nucleotide and the phosphate group of the adjacent nucleotide. The sugar is the 3′ end, and the phosphate is the 5′ end of each nucleotide. The phosphate group attached to the 5′ carbon of the sugar on one nucleotide forms an ester bond with the free

hydroxyl on the 3′ carbon of the next nucleotide. These bonds are called phosphodiester bonds, and the sugar-phosphate backbone is described as extending, or

growing, in the 5′ to 3′ direction when the molecule is synthesized. In double-stranded DNA, the molecular double-helix shape is formed by two linear sugar-phosphate backbones that

run opposite each other and twist together in a helical shape. The sugar-phosphate backbone is negatively charged and hydrophilic, which allows the DNA backbone to form

bonds with water.

Forms of DNA

The right-handed double-helical Watson – Crick Model for B-form DNA is the most commonly known DNA structure. In addition to this classic structure, several other forms of DNA have been observed. The helical structure of DNA is thus variable and depends on the sequence as well as the environment.

B-form DNA B-DNA is the Watson–Crick form of the double helix that most people are familiar with. They proposed two strands of DNA — each in a right-hand helix — wound around the same axis. The two strands

are held together by H-bonding between the bases (in anti-conformation). The two strands of the duplex are antiparallel and plectonemically coiled. The nucleotides arrayed in a 5′ to 3′

orientation on one strand align with complementary nucleotides in the 3′ to 5′ orientation of the opposite strand. Bases fit in the double helical model if pyrimidine on one strand is always paired with purine on the other.

From Chargaff’s rules, the two strands will pair A with T and G with C. This pairs a keto base with an amino base, a purine with a pyrimidine. Two H-bonds can form between A and T, and three can form between G and C.

These are the complementary base pairs. The base-pairing scheme immediately suggests a way to replicate and copy the genetic information.

34 nm between bp, 3.4 nm per turn, about 10 bp per turn 9 nm (about 2.0 nm or 20 Angstroms) in diameter. 34o helix pitch; -6o base-pair tilt; 36o twist angle

A-form DNA The major difference between A-form and B-form nucleic acid is in the confirmation of the deoxyribose sugar ring. It

is in the C2′ endoconformation for B-form, whereas it is in the C3′ endoconformation in A-form. A second major difference between A-form and B-form nucleic acid is the placement of base-pairs within the duplex.

In B-form, the base-pairs are almost centered over the helical axis but in A-form, they are displaced away from the central axis and closer to the major groove. The result is a ribbon-like helix with a more open cylindrical core in A-form.

Right-handed helix 11 bp per turn; 0.26 nm axial rise; 28o helix pitch; 20o base-pair tilt 33o twist angle; 2.3nm helix diameter

Z-form DNA Z-DNA is a radically different duplex structure, with the two strands coiling in left-handed helices and a pronounced

zig-zag (hence the name) pattern in the phosphodiester backbone. Z-DNA can form when the DNA is in an alternating purine-pyrimidine sequence such as GCGCGC, and indeed the G

and C nucleotides are in different conformations, leading to the zig-zag pattern. The big difference is at the G nucleotide.

It has the sugar in the C3′ endoconformation (like A-form nucleic acid, and in contrast to B-form DNA) and the guanine base is in the synconformation.

This places the guanine back over the sugar ring, in contrast to the usual anticonformation seen in A- and B-form nucleic acid. Note that having the base in the anticonformation places it in the position where it can readily form H-bonds with the complementary base on the opposite strand.

The duplex in Z-DNA has to accommodate the distortion of this G nucleotide in the synconformation. The cytosine in the adjacent nucleotide of Z-DNA is in the “normal” C2′ endo, anticonformation.

Discovered by Rich, Nordheim &Wang in 1984. It has antiparallel strands as B-DNA. It is long and thin as compared to B-DNA. 12 bp per turn; 0.45 nm axial rise; 45o helix pitch; 7o base-pair tilt -30o twist angle; 1.8 nm helix diameter

Other rare forms of DNAC-DNA

Formed at 66% relative humidity and in presence of Li+ and Mg2+ ions. Right-handed with the axial rise of 3.32A° per base pair 33 base pairs per turn Helical pitch 3.32A°×9.33°A=30.97A°. Base pair rotation=38.58°. Has a diameter of 19 A°, smaller than that of A-&B- DNA. The tilt of base is 7.8°

D-DNA Rare variant with 8 base pairs per helical turn These forms of DNA found in some DNA molecules devoid of guanine. The axial rise of 3.03A°per base pairs The tilt of 16.7° from the axis of the helix.

E- DNA Extended or eccentric DNA. E-DNA has a long helical axis rise and base perpendicular to the helical axis. Deep major groove and the shallow minor groove. E-DNA allowed to crystallize for a period time longer, the methylated sequence forms standard A-DNA. E-DNA is the intermediate in the crystallographic pathway from B-DNA to A-DNA.

Conditions Favoring A-form, B-form, and Z-form of DNA Whether a DNA sequence will be in the A-, B-or Z-DNA conformation depends on at least three conditions. The first is the ionic or hydration environment, which can facilitate conversion between different helical forms. A-DNA is favored by low hydration, whereas Z-DNA can be favored by high salt. The second condition is the DNA sequence: A-DNA is favored by certain stretches of purines (or pyrimidines),

whereas Z-DNA can be most readily formed by alternating purine-pyrimidine steps. The third condition is the presence of proteins that can bind to DNA in one helical conformation and force the DNA

to adopt a different conformation, such as proteins which bind to B-DNA and can drive it to either A-or Z forms. In living cells, most of the DNA is in a mixture of Aand B-DNA conformations, with a few small regions capable of

forming Z-DNA.

Why do different forms of DNA exist? There is simply not enough room for the DNA to be stretched out in a perfect, linear B-DNA conformation. In nearly

all cells, from simple bacteria through complex eukaryotes, the DNA must be compacted by more than a thousand fold in order even to fit inside the cell or nucleus.

Refined resolution of the structure of DNA, based on X-ray crystallography of short synthetic pieces of DNA, has shown that there is a considerable variance of the helical structure of DNA, based on the sequence. For example, a 200-bp piece of DNA can run as if it were more than 1000 bp on an acrylamide gel if it has the right sequence. The double helix is not the same uniform structure.