MOLECULAR STRUCTURE OF
NUCLEIC ACIDS

A Structure for Deoxyribose Nucleic Acid

W5 wish to suggest a structure for the salt
of deoxyribose nucleic acid (D.N.A.). This
structure has novel features which are of considerable
biological interest.

A structure for nucleic acid has already been
proposed by Pauling and Corey'. They kindly made
thoir manuscript available to us in advance of
publication. Their model consists of three inter-
twined 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 othor. (2) Some of the van der Waals
distances appear to be too small.

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

We wish to put forward a
radicaliy different structure for
the salt of deoxyribose nucleic
acid. This structure has two
helical chaina cach coiled round
the same axis (see diagram). We
have made the usual chemical
assumptions, namely, that each
chain consists of phosphate di-
ester groups joining 6-p-deoxy-
ribofuranose residues with 3’,5’
linkages. Tho two chains (but
not their bases) are related by a
dyad porpendicular 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
givin loosely resembles Fur-
berg’s? 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’, ane
sugar being roughly perpendi-
ular to the attached ako. There

 

This Qgure {fe purely
diagrammatic. The two
ribbons symbolize the
two phosphate—eugar
chains, and the hort-
zontal rods the pairs of
bases bolding the chains
together. The vertical
Nne maria the fibre axis

737

is & residue on cach chain every 3-4 A. in the z-direc-
tion. We have assumed an angle of 36° between
adjacent residues in the same chain, so that the
structure repeats after 10 residues on oach 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 fibro axis. They are joined
together in pairs, & 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
2-co-ordinates, One of the pair must be a purine and
the other a pyrimidine for bonding to occur. The
hydrogen, bonds are made as follows : purine position
1 to pyrimidine position 1; purine position 6 to
pytimidine 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 con-
figurations) 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)... | oo

In other words, if an adenine forms one member of
& pair, on cither chain, then on these assumptions
the other member must be thymine ;. similarly for
guanine and cytosine. The sequence of bases on &
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 seqtence on the other
chain is automatically determined. §... © *

It has been found experimentally* 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. ee .

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

The previously published X-ray data’ on deoxy-
ribose 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
againat 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. stereo-
chemical arguments. gp

It has not escaped our notice that the’ specific
pairing we have postulated immediately suggests’ 4
possible copying mechaniam for the genstio material.

Full details of the structure, indluding the con-
ditions assumed in building it, with a set
of co-ordinates for the atoms, will. be published
elsewhere.

We are muoh indebted to Dr. Jerry Donohue for
constant advice and oriticiam, cspecially on inter-
atomic distances. We have also beon stimulated by
a knowledge of the general nature of the lished
experimental resulta and ideas of Dr. M. H. .F.
Wilkins, Dr. R. E. Franklin and their co-workers at
738 NATURE

King’s College, London. One of us (J.D. W. ) has been
aided by a fellowship from the National Foundation

for Infantile Paralysis.
J. D. Watson
¥. H. C. Crrox
Medical Research Council Unit for the
Study of the Molecular Structure of
-. . Biological Systems,
Cavendish Laboratory, Cambridge.

April 2.
t Pauling, J I, and Corey, R B. B.. s, Nature, 171, 346 (1958); Proe. U.S.
cad. Set., 39, 84 (1953).

« Fusberg. ‘a ‘Acts Chem. Scand., 6, 634 (1952).
* Chargaff, E., for references see Zamcohof, S., Brawerman, G., and
Chargaff, E.., Biochim. et Biophys. Acta, B, 402 (1952).
“Wyatt. G. B., J. Gen. Physiol., 38, 201 (1952).
* Astbury, Ww. T., en. Soc. Exp. Biot. 1, Nucleic Acid, 66 (Camb.
ewiteins: M. » and Randall, J. T., Biochim. et Biophys. Acta,
_ 16, 192 (a8).

‘April 25, 1953

Vor. 171