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Resumé:
V kigger på artiklen bag århundreds største biologiske opdagelse. Offentliggørelsen af DNA´s struktur i 1953 var en enestående videnskabelig bedrift. Målt med samtidens øjne var det en opgave, man først troede det var muligt at løse ved udgangen af det 20 århundredet. Watson og Crick´s model for strukturen af DNA gav samtidigt svaret på, hvorledes egenskaber nedarves fra generation til generation. Idag, et lille stykke ind i det 21 århundrede forventes det, at man i år 2003 kender samtlige bogstaver og deres rækkefølge i den menneskelige arvemasse. Vi har endnu kun set begyndelsen på den biologiske revolution der startede med publiceringen af denne artikel.

MOLECULAR STRUCTURE OF NUCLEIC ACIDS: A STRUCTURE FOR DEOXYRIBOSENUCLEIC ACID

We wish to propose a structure for the salt of deoxyribosenuclein acid (DNA). This structure has novel features which are of considerable biological interest.

Nu følger en kort diskussion af Linus Pauling´s DNA model, som Watson og Crick afviser som utilfredstillende. Herefter beskriver de deres egen model.

We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid. This structure has two helical chains each coiled round the same axis. We have made the usual chemical assumptions, namely, that each chain consists of phosphate diester groups joining ß-D-deoxyribofuranose residues with 3´,5´ linkages. The two chains (but not their bases) are related by a dyad perpendicular to the fibre axis. Both chains follow right-handed helices, but owing to the dyad the sequences of the atoms in the two chains run in opposite directions. Each chain loosely resembles Furbergs´s (2) model No. 1; 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 Å in the z-direction. We have assumed an angle of 36 degrees between adjacent residues in the same chain, so that the structure repeats after 10 residues on each chain, that is after 34 Å. the distance of a phosphorous atom from the fibre axis is 10 Å. As the phosphates are on the outside, cations have easy access to them.

The structure is an open one, and it´s 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 hold together by the purine and the pyrimidine bases. The planes of the bases are perpendicular to fibre axis. They are 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 z-co-ordinates. One of the pair must be apurine and the other a pyrimidine for bonding to occur. The hydrogen bonds are made as follows: purine position 1 to pyrimidine position1; purine position 6 to pyrimidine 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 configuration) it is found that only specific pairs of bases can bond together. These pairs are: adenine (purine) with thymine (pyrimidine), and guanidine (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 a thymine, similarly for guanine and cytosine. The sequnce 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 experimentally(3,4) 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 in place of a deoxyribose, as the extra oxygen atom would make too close a van der waals contact.

The previously published X-ray data (5,6) on deoxyribose nucleic acid are insuffient 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 copying mechanism for the genetic material.

Artiklen slutter med at takke kollegaer for hjælp og råd med arbejdet.

J.D. Watson
F.H.C. Crick
Medical Research Counsil Unit for the Study of
Molecular Structure of Biological Systems
Cavendish Laboratory, Cambridge.

D.Watson and F.H.C.Crick: Molecular structure of nucleic acids: a structure for deoxyribosenucleic acid. Nature, 1953, Vol. 171 No. 4356, pp. 737-8.