Molecular Structure Of Nucleic Acids

A structure for Deoxyribose Nucleic Acid

Wc wish to suggest a structure tor the salt of deoxyribose nucleic acid {D.N.A.), This structure has novel features which arc of considerable biological interest,

A structure for nucleic acid has already been proposed by Pauling and Corey1. They kindly made their manuscript available to us in advance of publication. Their model consists of three intertwined chains, with the phosphates near the fibre axis, and the bases on the outside. In our opinion, this structure is unsatisfactory for two reasons: (1) We believe that the material which gives the X-ray diagrams is the salt, not the free acid. Without the acidic hydrogen atoms it is not clear what forces would hold the structure together, especially as the negatively charged phosphates near the axis will repel each other. (2) Some of ihc van der Waals distances appear to be too small.

Another three-chain structure has also been suggested by Fräser (in the press). In his model the phosphates are on the outside and the bases on the inside, linked together by hydrogen bonds, This structure as described is rather ill-defined, and for this reason we shall not comment on it.

We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid. This structure has two he!teal chains each coiled round the same axis (sec diagram). We have made the usual chemical assumptions, namely, that each chain consists of phosphate diester groups joining j3-D-deoxyrihofuranose residues with 3', 5' linkages. The two chains (hut not their bases) are related by a dyad perpendicular to the fibre axis. Both chains follow right-handed gelices, but owing to the dyad the sequences of the atoms in the two chains run in opposite directions. Bach chain loosely resembles FurbergV model No. I ■ that is the bases are on the inside of the helix and the phosphates on the outside. The configuration of the sugar and the atoms near it is close to Furberg's "standard configuration', the sugar being roughly perpendicular to the attached base. There is a residue on each chain every 3-4. A, in the ¿-direction. We have assumed an angle of 36° between adjacent residues in the same chain, so that the structure repeats after 10 residues on each chain, that is, after 34 A. The distance of a phosphorus atom from the fibre axis is 10 A, As the phosphates are on the outside, cations have easy access to them.

The structure is an open one. and its water content is rather high. At lower water contents we would expect the bases to tilt so that the structure could become more compact.

The novel feature of the structure is the manner in which the two chains are held together by the purine and pyrimidine bases, The planes of the bases are perpendicular to the fibre axis. They arc joined together in pairs, a single base from one chain being hydrogen-bonded to a single base from the other chain, so that the two lie side by side with identical ¿-co-ordinates. One of the

Tliis Tigurc is purely diagrammatic The Two ribbons symbolize the two phosphate sugar chain*, and (he hiifiïnntjl roth Ihc pairv of holding Uie chata» (ngrthcr The vertical line rnark.\ ihe libre HM>

Tliis Tigurc is purely diagrammatic The Two ribbons symbolize the two phosphate sugar chain*, and (he hiifiïnntjl roth Ihc pairv of holding Uie chata» (ngrthcr The vertical line rnark.\ ihe libre HM>

pair must be a purine and the other a pyrimidine for bonding to occur. The hydrogen bonds are made as follows: purine position I to pyrimidine position 1; purine position 6 to pyrmidine position 6.

If it is assumed that the bases only occur in the structure in the most plausible tautomeric forms (that is, with the keto rather than the enol configurations) it is found that only specific pairs of bases can bond together. These pairs are: adenine (purine) with thymine (pyrimidine). and guanine (purine) with cytosine (pyrimidine).

In other words, if an adenine forms one member of a pair, on either chain, then on these assumptions the other member must be thymine; similarly for guanine and cytosine. The sequence of bases on a single chain does not appear to be restricted in any way. However, if only specific pairs of bases can be formed, it follows that if the sequence of bases on one chain is given, then the sequence on the other chain is automatically determined.

It has been found experimentally3'4 that the ratio of the amounts of adenine to thymine, and the ratio of guanine to cytosine. are always very close to unity for deoxyribose nucleic acid.

It is probably impossible to build this structure with a ribose sugar in placc of the deoxyribose. as the extra oxygen atom would make too close a van der Waals contact.

The previously published X-ray data3,4 on deoxyribose nucleic acid are insufficient for a rigorous test of our structure. So far as we can tell. It is roughly compatible with the experimental data, but it must be regarded as unproved until it has been checked against more exact results. Some of these are given in the following communications. We were not aware of the details of the results presented there when we devised our structure, which rests mainly though not entirely on published experimental data and stereochemical arguments,

It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material,

Full details of the structure, including the conditions assumed in building it. together with a set of co-ordinates for the atoms, will be puhlished elsewhere.

We are much indehted to Dr. Jerry Donohue for constant advice and criticism, especially on inter-atomic distances. We have also been stimulated by a knowledge of the general nature of the unpublished experimental results and ideas of Dr. M, H, F, Wilkins, Dr. R. E. Franklin and their co-workers at King's College, London. One of us (J. D. W'.) has been aided by a fellowship from the National Foundation for Infantile Paralysis.

Medical Research Council Unit for the Study of the Molecular Structure of

Biological Systems, Cavendish Laboratory, Cambridge.

April 2.

'Pauling. L.. and Corey, R. B., Nature. 171, 346(1953); Proc, U.S. Nal.

Acad, St/., 39, 84 (1953) JFurberg. S., Acta Chetn. ScartcJ., 6, 634 (1952). 'Chargaff. E,, lor references see Zamenhof, S.( Brawerman, G., and

Ctargaff, E.. BUntiim. et Biopftys. Acta. 9, 402 (1952). ♦Wyatt. G, R., J. Gen. Physiol,, 36, 201 (1952) *Astbury. W, T . Symp, Soe. Exp Biol. 1, Nucleic Acid. 66 (Camb.

Univ. Press. 1947), 'Wilkins. M H. F-. and Randall, J, T., Biochim. ef Btophys. Acta, 10. 192 (1953).

FIGURE 3.08 DNA Is a Double Helix

This one-page paper published in Nature described the now-famous double helix. J. D. Watson & F. H. C. Crick, Molecular Structure of Nucleic Acids, A Structure for Deoxyribose Nucleic Acid, Nature 171 (1953) 737.

Complementary Strands Reveal the Secret of Heredity 59

In 2003 the Double Helix celebrated its 50th anniversary. In Great Britain, the Royal Mail issued a set of five commemorative stamps illustrating the double helix together with some of the technological advances that followed, such as comparative genomics and genetic engineering. In addition, the Royal Mint issued a £2 coin depicting the DNA double helix itself (Fig. 3.09).

FIGURE 3.09 Double Helix—50th Anniversary Coin

A £2 coin commemorating the discovery of the double helix was issued in 2003 by Great Britain.

FIGURE 3.09 Double Helix—50th Anniversary Coin

A £2 coin commemorating the discovery of the double helix was issued in 2003 by Great Britain.

or nitrogen as the atoms that carry the hydrogen, giving three alternative arrangements: O-H-O, N-H-N and O-H-N.

Each base pair consists of one larger purine base paired with a smaller pyrimidine base. So, although the bases themselves differ in size, all of the allowed base pairs are the same width, providing for a uniform width of the helix. The A-T base pair has two hydrogen bonds and the G-C base pair is held together by three, as shown in Figure 3.10. Before the hydrogen bonds form and the bases pair off, the shared hydrogen atom is found attached to one or the other of the two bases (shown by the complete lines in Fig. 3.10). During base pairing, this hydrogen also bonds to an atom of the second base (shown by the dashed lines).

Although RNA is normally single-stranded, many RNA molecules fold up, giving double-stranded regions. In addition, a strand of RNA may be found paired with one of DNA under some circumstances. Furthermore, the genome of certain viruses consists of double-stranded RNA (see Ch. 17). In all of these cases, the uracil in RNA will base pair with adenine. Thus the base-pairing properties of the uracil found in RNA are identical to those of the thymine of DNA.

Due to the rules for base-pairing, the sequence of a DNA strand can be deduced if the sequence of its partner is known.

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