DNA Structure : Double helix

In the double helix, the two chains are coiled around a common axis called the helical axis. The chains are paired in an antiparallel manner (that is, the  5′-end of one strand is paired with the 3′-end of the other strand), as shown in Figure 1. In the DNA helix, the hydrophilic deoxyribose-phosphate backbone of each chain is on the outside of the molecule, whereas the hydrophobic bases are stacked inside. The overall structure resembles a twisted ladder. The spatial relationship between the two strands in the helix creates a major (wide) groove and a minor (narrow) groove. These grooves provide access for the binding of regulatory proteins to their specific recognition sequences along the DNA chain. [Note: Certain anticancer drugs, such as dactinomycin (actinomycin D), exert their cytotoxic effect by intercalating into the narrow groove of the DNA double helix, thereby interfering with DNA (and RNA) synthesis.]

Figure 1: DNA double helix, illustrating some of its major structural features.
1. Base-pairing: The bases of one strand of DNA are paired with the bases of the second strand, so that an adenine (A) is always paired with a thymine (T), and a cytosine (C) is always paired with a guanine (G). [Note: The base pairs are perpendicular to the helical axis (see Fig.1).] Therefore, one polynucleotide chain of the DNA double helix is always the complement of the other. Given the sequence of bases on one chain, the sequence of bases on the complementary chain can be determined (Fig. 2). [Note: The specific base-pairing in DNA leads to the Chargaff rule, which states that in any sample of dsDNA, the amount of A equals the amount of T, the amount of G equals the amount of C, and the total amount of purines (A + G) equals the total amount of pyrimidines (T + C).] The base pairs are held together by hydrogen bonds: two between A and T and three between G and C (Fig. 3). These hydrogen bonds, plus the hydrophobic interactions between the stacked bases, stabilize the structure of the double helix.

Figure 2: Two complementary DNA sequences. T = thymine; A = adenine; C = cytosine; G = guanine.

Figure 3: Hydrogen bonds between complementary bases.
2. DNA strand separation: The two strands of the double helix separate when hydrogen bonds between the paired bases are disrupted. Disruption can occur in the laboratory if the pH of the DNA solution is altered so that the nucleotide bases ionize, or if the solution is heated. [Note: Covalent phosphodiester bonds are not broken by such treatment.] When DNA is heated, the temperature at which one half of the helical structure is lost is defined as the melting temperature (T_m). The loss of helical structure in DNA, called denaturation, can be monitored by measuring its absorbance at 260 nm. [Note: ssDNA has a higher relative absorbance at this wavelength than does dsDNA.] Because there are three hydrogen bonds between G and C but only two between A and T, DNA that contains high concentrations of A and T denatures at a lower temperature than does G- and C-rich DNA (Fig. 4). Under appropriate conditions, complementary DNA strands can reform the double helix by the process called renaturation (or, reannealing). [Note: Separation of the two strands over short regions occurs during both DNA and RNA synthesis.]

Figure 4: Melting temperatures (Tm) of DNA molecules with different nucleotide compositions. A = adenine; T = thymine; G = guanine; C = cytosine.
3. Structural forms: There are three major structural forms of DNA: the B form (described by Watson and Crick in 1953), the A form, and the Z form. The B form is a right-handed helix with 10 base pairs (bp) per 360° turn (or twist) of the helix, and with the planes of the bases perpendicular to the helical axis. Chromosomal DNA is thought to consist primarily of B-DNA (Fig. 5 shows a space-filling model of B-DNA). The A form is produced by moderately dehydrating the B form. It is also a righthanded helix, but there are 11 bp per turn, and the planes of the base pairs are tilted 20° away from the perpendicular to the helical axis. The conformation found in DNA–RNA hybrids  or RNA–RNA double-stranded regions is probably very close to the A form. Z-DNA is a left-handed helix that contains 12 bp per turn (see Fig. 5). [Note: The deoxyribose-phosphate backbone zigzags, hence, the name Z-DNA.]
Stretches of Z-DNA can occur naturally in regions of DNA that have a sequence of alternating purines and pyrimidines (for example, poly GC). Transitions between the B and Z helical forms of DNA may play a role in regulating gene expression.

Figure 5: Structures of B-DNA and Z-DNA.