DNA Double helix

DNA double helix : 
Although the primary structure of DNA represents a long polynucleotide chain, it does not provide any clue how the essential tasks of a genetic material, i.e., packing and storing information, releasing information in a definite and regulated manner, replicating itself and allowing mutational changes for evolution can be accomplished by this macromolecule. The answer lies to the secondary structure adopted by DNA in the

biological environment to perform each of these functions. Elucidation of the secondary double helical structure of DNA, considered as the most important discovery of biological science goes to the credit of James Watson and Francis Crick, who solved the riddle of life in 1953. The race to the discovery of DNA double helix began in late 1940s, invoLving many reputed scientists of the world. E. Chargaff in 1940s after comparing base composition of many species noted that purine and pyrimidine arc present in equimolar ratio, and concentration of adenine is equal to thyminewhile concentration of guaninc is equal to cytosine in all these
organisms. At about same time, DNA could be made crystalline and X-ray crystallographic analyses were being performed to understand the structure of DNA by Astbury, R. Franklin and M. Wilkins. One of the X-ray photographs of DNA by Franklin, famous as ‘photograph 51’ showed that crystalline DNA is a helical structure with a regular turn and helix diameter of 20 A. Kinetic studies on DNA in solution suggested that DNA might have hydrogen bonds. Based on these information, Watson and Crick proposed the structure of B-DNA, s’hich is a right handed double helix containing two polvnucleotide chains intertwined around each

other through a helix axis. Two most important criteria of this structure are base corn plensentarity and antipnrnlklisrn that explain the biological utility of DNA. Two chains of the helix are antiparallel to each other, i.e., they have opposite polarity. This helps in positioning the sugar phosphate backbone towards
outside of the helix, while the bases remain inside. The nitrogenous bases in one chain are complementary to that of the other chain being joined by hydrogen bonding. Adeninc in on chain always pairs with thymine with two hydrogen bonds, while guanine pairs with cytosine with three hydrogen bonds. In this way, if the sequence of bases of one chain is known, the composition of the other chain can definitely be predicted. Exploiting these features, DNA replicates itself, disseminates information by synthesizing RNA and allows mutational and recombinational changes to account for genetic variability. The double helix has a constant diameter of 20 A, which is sufficient to fit one purine-pyrimidine hydrogen bonding combination. Each

nucleotide of the chain shos’s a restricted rotation of 36° due to phosphodiester bridge formation. A complete revolution of 360° involves 10 base pairs. The distance that a double helix covers in one complete turn is 34 A, distance between each base pair being 3.4 A. The right handed B-DNA is the most abundant DNA found in nature, although slight variations exist from the proposed Watson-Crick structure. The B-DNA found in nature has about 10.5 base pairs per turn of helix. Alternate forms of DNA can be
found depending on the relative humidity and salt concentration of the environment as well as the composition of the nucleotides. The A-DNA, induced under low relative humidity is a right handed fatty helix with diameter about 26 A, ii base pairs per turn of helix and a helical twist of 33° per base rise and a helix

pitch (distance per complete turn) of 28 A. This helical structure is more common in RNA-DNA hybrid structures. A further unusual structure is left handed Z-DNA, which forms when alternate purine-pyrimidine dinucleotide repeats are present developing into a zigzag structure with 12 base pairs per turn, twist of 60’ per dimer and a helix pitch of 45 A. Although hydrogen bond formation between bases is essential for double helix formation, major stability of the double helical structure of DNA is provided by hydrophobic interactions. The bases of DNA are hydrophobic in nature. For this nature, energetically favorable
stacking of bases in the inside core of double helix and presence of charged phosphate group on the outer surface provides the real stability of the double helix. In case of single stranded DNA or RNA also the bases have a tendency to be grouped or stacked together. One of the important features of double helix that helped

Watson and Crick to provide an explanation of mutation in DNA is the tautomeric shifts in the base composition. The two bases, guanine and thymine exist in ‘keto’ form in normal pH, while adenine and cytosine remain in ‘amino’ form. In this condition, Watson-Crick base pairing between (A=T; GC) is observed. However, under higher pH, the keto form shows a reversible tautomeric shift towards enol form. At this condition GT and A=C base pairing are observed. If replication occurs during such changes, wrong nucleotide will be incorporated in the replicated DNA strand leading to mutation. Denatu ration of DNA double helix by alkaline treatment also works on the same principle. On treatment with alkali, pH of the solution increases, destabilizing the A=T and GC base pair and separations of two strands.