DNA is a double helix

KEY TERMS:

• Base pairing describes the specific (complementary) interactions of adenine with thymine or of guanine with cytosine in a DNA double helix (thymine is replaced by uracil in double helical RNA).
• Complementary base pairs are defined by the pairing reactions in double helical nucleic acids (A with T in DNA or with U in RNA, and C with G).
• Antiparallel strands of the double helix are organized in opposite orientation, so that the 5 end of one strand is aligned with the 3 end of the other strand.
• The minor groove of DNA is 12Å across.
• The major groove of DNA is 22Å across.
• A helix is said to be right-handed if the turns runs clockwise along the helical axis.
• B-form DNA is a right-handed double helix with 10 base pairs per complete turn (360°) of the helix. This is the form found under physiological conditions whose structure was proposed by Crick and Watson.
• A stretch of overwound DNA has more base pairs per turn than the usual average (10 bp = 1 turn). This means that the two strands of DNA are more tightly wound around each other, creating tension.
• A stretch of underwound DNA has fewer base pairs per turn than the usual average (10 bp = 1 turn). This means that the two strands of DNA are less tightly wound around each other; ultimately this can lead to strand separation. 

KEY CONCEPTS:

• The B-form of DNA is a double helix consisting of two polynucleotide chains that run antiparallel.
• The nitrogenous bases of each chain are flat purine or pyrimidine rings that face inwards and pair with one another by hydrogen bonding to form A-T or G-C pairs only.
• The diameter of the double helix is 20 Å, and there is a complete turn every 34 Å, with 10 base pairs per turn.
• The double helix forms a major (wide) groove and a minor (narrow) groove.

 The observation that the bases are present in different amounts in the DNAs of different species led to the concept that the sequence of bases is the form in which genetic information is carried. By the 1950s, the concept of genetic information was common: the twin problems it posed were working out the structure of the nucleic acid, and explaining how a sequence of bases in DNA could represent the sequence of amino acids in a protein.

Three notions converged in the construction of the double helix model for DNA by Watson and Crick in 1953:

• X-ray diffraction data showed that DNA has the form of a regular helix, making a complete turn every 34 Å (3.4 nm), with a diameter of ~20 Å (2 nm). Since the distance between adjacent nucleotides is 3.4 Å, there must be 10 nucleotides per turn.
• The density of DNA suggests that the helix must contain two polynucleotide chains. The constant diameter of the helix can be explained if the bases in each chain face inward and are restricted so that a purine is always opposite a pyrimidine, avoiding partnerships of purine-purine (too wide) or pyrimidine-pyrimidine (too narrow).
• Irrespective of the absolute amounts of each base, the proportion of G is always the same as the proportion of C in DNA, and the proportion of A is always the same as that of T. So the composition of any DNA can be described by the proportion of its bases that is G + C. This ranges from 26% to 74% for different species.

Watson and Crick proposed that the two polynucleotide chains in the double helix associate by hydrogen bonding between the nitrogenous bases. G can hydrogen bond specifically only with C, while A can bond specifically only with T. These reactions are described as base pairing, and the paired bases (G with C, or A with T) are said to be complementary.

The model proposed that the two polynucleotide chains to run in opposite directions (antiparallel), as illustrated in Figure 1.8. Looking along the helix, one strand runs in the 5→3 direction, while its partner runs 3→5 (Watson and Crick, 1953; Wilkins, Stokes, and Wilson, 1953; Watson and Crick, 1953).

The sugar-phosphate backbone is on the outside and carries negative charges on the phosphate groups. When DNA is in solution in vitro, the charges are neutralized by the binding of metal ions, typically by Na⁺. In the cell, positively charged proteins provide some of the neutralizing force. These proteins play an important role in determining the organization of DNA in the cell.

The bases lie on the inside. They are flat structures, lying in pairs perpendicular to the axis of the helix. Consider the double helix in terms of a spiral staircase: the base pairs form the treads, as illustrated schematically in Figure 1.9. Proceeding along the helix, bases are stacked above one another, in a sense like a pile of plates.

Each base pair is rotated ~36° around the axis of the helix relative to the next base pair. So ~10 base pairs make a complete turn of 360°. The twisting of the two strands around one another forms a double helix with a minor groove (~12 Å across) and a major groove (~22 Å across), as can be seen from the scale model of Figure 1.10. The double helix is right-handed; the turns run clockwise looking along the helical axis. These features represent the accepted model for what is known as the B-form of DNA.

It is important to realize that the B-form represents an average, not a precisely specified structure. DNA structure can change locally. If it has more base pairs per turn it is said to be overwound; if it has fewer base pairs per turn it is underwound. Local winding can be affected by the overall conformation of the DNA double helix in space or by the binding of proteins to specific sites.