To the knowledge of the chemical makeup of the nucleotides and their linkages in a DNA strand, Watson and Crick added results from earlier physical studies indicating that DNA is a long molecule. They also relied on important information from X-ray diffraction studies by Rosalind Franklin implying that DNA molecules form a helix with a simple repeating structure. Analysis of the pattern of X-rays diffracted from a crystal of a molecule can indicate the arrangement of atoms in the molecules.

With these critical pieces of information in hand, Watson and Crick set out to build a model of DNA that could account for the results of all previous chemical and physical experiments, using sheet metal cutouts of the bases and wire ties for the sugar–phosphate backbone. After many false starts and much disappointment, they finally found a structure that worked. They realized immediately that they had made one of the most important discoveries in all of biology, and that day, February 28, 1953, they lunched at the Eagle, a pub across the street from their laboratory, where Crick loudly pronounced, “We have discovered the secret of life.” The Eagle is still there in Cambridge, England, and sports on its wall a commemorative plaque marking the table where the two ate.

Why all the fuss (and why the Nobel Prize nine years later)? First, let’s look at the structure, and you will see that the structure itself tells you how DNA carries and transmits genetic information. The Watson–Crick structure, now often called the double helix, is shown in Fig. 3.8. Fig. 3.8a is a space-filling model, in which each atom is represented as a color-coded sphere. The big surprise of the structure is that it consists of two DNA strands like those in Fig. 3.7, each wrapped around the other in the form of a helix coiling to the right, with the sugar–phosphate backbones winding around the outside of the molecule and the bases pointing inward. In the double helix, there are 10 base pairs per complete turn, and the diameter of the molecule is 2 nm, a measurement that is hard to relate to everyday objects, but it might help to know that the cross section of a bundle of 100,000 DNA molecules would be about the size of the period at the end of this sentence. The outside contours of the twisted strands form an uneven pair of grooves, called the major groove and the minor groove. These grooves are important because proteins that interact with DNA often recognize a particular sequence of bases by making contact with the bases via the major or minor groove or both.

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Importantly, the individual DNA strands in the double helix are antiparallel, which means that they run in opposite directions. That is, the 3′ end of one strand is opposite the 5′ end of the other. In Fig. 3.8a, the strand that starts at the bottom left and coils upward begins with the 3′ end and terminates at the top with the 5′ end, whereas its partner strand begins with its 5′ end at the bottom and terminates with the 3′ end at the top.

Fig. 3.8b shows a different depiction of double-stranded DNA, called a ribbon model, which clearly shows the sugar–phosphate backbones winding around the outside with the bases paired between the strands. The ribbon model of the structure closely resembles a spiral staircase, with the backbones forming the banisters and the base pairs the steps. If the amount of DNA in a human egg or sperm (3 billion base pairs) were scaled to the size of a real spiral staircase, it would reach from Earth to the moon.

Note that, as shown in Fig. 3.8b, an A in one strand pairs only with a T in the other, and G pairs only with C. Each base pair contains a purine and a pyrimidine. This precise pairing maintains the structure of the double helix since pairing two purines would cause the backbones to bulge and pairing two pyrimidines would cause them to narrow. The pairing of one purine with one pyrimidine preserves the distance between the backbones along the length of the entire molecule.

Because they form specific pairs, the bases A and T are said to be complementary, as are the bases G and C. The formation of only A–T and G–C base pairs means that the paired strands in a double-stranded DNA molecule have different base sequences. The strands are paired like this:

5′-ATGC-3′
3′-TACG-5′

Where one strand has the base A, the other strand across the way has the base T, and where one strand has a G, the other has a C. In other words, the paired strands are not identical but complementary. Because of the A–T and G–C base pairing, knowing the base sequence in one strand immediately tells you the base sequence in its partner strand.

Why is it that A pairs only with T, and G only with C? Fig. 3.9 illustrates the answer. The specificity of base pairing is brought about by hydrogen bonds that form between A and T (two hydrogen bonds) and between G and C (three hydrogen bonds). A hydrogen bond in DNA is formed when an electronegative atom (O or N) in one base shares a hydrogen atom (H) with another electronegative atom in the base across the way. Hydrogen bonds are relatively weak bonds, typically 5% to 10% of the strength of covalent bonds, and can be disrupted by high pH or heat. However, in total they contribute to the stability of the DNA double helix.

An almost equally important factor contributing to the stability of the double helix is the interactions between bases in the same strand (Fig. 3.10). This stabilizing force is known as base stacking, and it occurs because the nonpolar, flat surfaces of the bases tend to group together away from water molecules, and hence stack on top of one another as tightly as possible.