Medical and Health Annual (1982)

Date:
1980-1981
Reference:
PP/CRI/H/7/1
Catalogue details

Licence: In copyright

Credit: <i>Medical and Health Annual</i> (1982). Source: Wellcome Collection.

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    68 i • macromolecules: nucleic acids STRUCTURE A is the crystalline form of DNA found at rela tively low humidity. This X-ray photograph is by H. R. Wilson. broad arrangement of the molecule-must be independent of the exact sequence of the bases, and it was therefore thought that the bases play no part in holding the structure together. As we shall see, this turned out to be wrong. The early X-ray pictures showed a third intriguing fact: namely, that the repeats in the crvstallographic pattern c ame at much longer intervals than the chemical repeat units in the molecule. The distance from one phosphate to the - next cannot be more than about seven Angstroms, yet the crvstallographic re peat came at intervals of 28 Angstroms <n the crystalline form and 34 Angstroms in the paracrystalline form; that is, the chemical unit repeated several times be fore the structure repeated crystal- lographically. J. D. Watson and I, working in the Medical Research Council Unit in the Cavendish Laboratory at Cambridge, were convinced that we could get some where near the DNA structure by build ing scale models based on the X-ray patterns obtained bv M. H. F. Wilkins, Rosalind Franklin and their co-workers at Kings' College, London. A great deal is known about the exact distances be tween bonded atoms in molecules, about the angles between the bonds and about the size of atoms—the so-called van der Waals' distance between adjacent non- bonded atoms. . This information is easy to embody in scale models. The prob lem is rather like a three-dimensional jig saw puzzle with curious pieces joined together by rotatable joints (single bonds between atoms). The Helix To get anywhere at all we had to make some assumptions. The most im portant one had to do with the fact that the crystallographic repeat did not coin cide with the repetition of chemical units in the chain but came at much longer intervals. A possible explanation was that all the links in the chain were the same but the X-rays were seeing every tenth link, say, from the same angle and the others from different angles. What sort of chain might pro duce this pattern? The answer was easy: the chain might be coiled in a helix. (A helix is often loosely called a spiral; the distinction is that a helix winds not around a cone but around a cylinder, as a winding staircase usually does.) The distance between crvstallographic re peats would then correspond to the dis tance in the chain between one turn of the helix and the next. We had some difficulty at first be cause we ignored the bases and tried to work only with the phosphate-sugar backbone. Eventuallv we realized that we had to take the bases into and this led us quickly to a structure which we now believe to be correct in its broad outlines. This particular model contains a pair of DNA chains wound around a com mon axis. The two chains are linked to gether by their bases. A base on one chain is joined by very weak bonds to a base at the same level on the other chain, and all the bases are paired off in this way right along the structure. In the diagram opposite, the two rib bons represent the phosphate-sugar chains, and the pairs of bases holding them together are svmbolized as hori zontal rods. Paradoxically, in order to make the structure as symmetrical as possible we had to have the two chains run in opposite directions; that .is, the sequence of the atoms goes one wav in one chain and the opposite way in the other. Thus the figure looks exactly the same whichever end is turned up. Now we found that we could not ar range the bases any way we pleased; the four bases would fit into the struc ture only in certain pairs. In any pair there must always be one big one (pu rine) and one little one (pyrimidine). A pair of pvrimidines is too short to bridge the gap between the two chains, and a pair of purines is too big to fit into the space. At this point we made an additional assumption. The bases can theoretically