A 8TRUCTURIE: FOR D.N.A,

We wish to suggest a structure forddeoxyribose nucleic
acid (DJLA.).  This structure has novel features which are
of considerable biological interest*

A structure f;r nucleic acid has already been proposed by
Pauling and Corey.  They kindly made their manuscript available
to us Sn advance of publication,  Their model consists of three
intertwined chains, with the phosphates near the ffbre axis,
and the bases on the outside.  In our opinion this structure
is unsatisfactory for two reasons:

1.  We believe that the material which gtves the X-ray
  diagrams is the salt, not the free acid. Without the
  acidic hydrogen atom& ft is .not clear what forces
  would hold the structure together, especially as the
  negatively charged phosphates near the axis will
  repel each other.

2.  $ome of the van der Waals distances appear to be too
   small.

   Another three-chain structure has recently been suggested
                                                                           I
by Fraser. 9 in higt model the phosphates are on the outs'ide,
                                                                           .;>,
and the bases on the  inside 9
& linked tog        drogen bondsa  This structure as

described is       ill-defined, and for this reasonwe
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 helical chains each coiled round the same axis (see figure).
We have made the usual chemical assumptions, namely that each
chain consists of phosphate di-ester groups joining(3-D-deoxyribo-


-2-

fbranosa residues with 3'; 5' linkages, The two chafns (but not
their bases) are related by a dyad perpendicular to the fibre
axis e  Both chafns Follow right-handed helices, but owing to the
dyad the sequences of the atoms in the two chains run in
opposite directionsr                            t 2
            Each chain loosely resembles Furberg s
model MO. 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
confTigurationt* B the sugar being roughly perpendicular to the
atta -ched base',,  There is a residue on each chain every 3@4 8`
in the z direction.  We have assumed an angle of 36' between
adjacent residues in the same chain, so that the etmacture
repeats after 10 residues on each chain, that is, after 34 8.
The distance of a phosphorus atom from the fibre axis is 10 2.
AS the phosphates are on the outside, cations have e&y access
to them,                       i
                                                        ,' t

The structure is an open one, and its water c&tent is

rather high,  At lower water contents we would expect the bases
to tilt so that the structure could become more dompact.

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 are joined together fn pairs, a single base from ," ,:
one chain being hydrogen-bonded to a single base from the other ;1

chain, so that the two lie side-by-side with identical z             yp
                                                          ($
co-ordinates* One of the pair must be a purfne 6nd. the other 4:
pyrimidine for bonding to occur.  The hydrogen bonds are made '

as follows~

Purlne position 1 to gyrimidine position 3.
Eurins position 6 to pyrfmidine position 6
Tf it is assumed that the bases only OCCUF in the structure


in the most plausible tautomwic forms, (that is with the keto
rather than the enol configurations) it is found that only
Slpecifio pairs of bases can bond together,,  These pairs aret

Adenine (purine) with Thymine (pyrimidina)
Guanine (purine) with Cytosine (pyrimidine)

Tn othece wordsfi 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 wayI  However, if only saeci,fic pairs of
bases can be formed it follows that if, the sequence of bases
on one chain is given, then the seqlience on the other chain is
automtically determined+

   It has been founll 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 D.&A.

   ft is probably impossible to build this structure with a
ribose sugar in place of the deoxyribose, as the extra oxygen
atom would xrw.ke tuo close a van der Waals contact*

   The previously published X-ray data 5*6 on D&A, are
insufficient for a vigorous test of our structure. As far as
we can tell. it is roughly compatibl8 with the experimental
data, but it must be regarded as unproved until it has been
checked against more exact resul.ts,  Some of these are given
in the adjoining publications 7,8 . 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 QUF notice that the specific pairing

we have postulated immediately a-uggests a possible copying
mechanism for the genetio material*

Full details of the struc%re, including the conditions

assumed in building it, together with a set of co-ordinates for
the atoms, will be published elsewhere,

We are heavily indebted to Dr. Jerry Donohue for constant

advice and criticism, especially 0;t-a inter-atomic distances. We
have also been stimulated by aAsyledgTtic$ the general nature
                                              , I'*
of the unpublished experimental~results~of`Dr, M.H.F. Wilkins,
Dr. R, E* Franklin and their co-workers at Kings College, London.
One of us (J,D,W,) has been aided by a Fellowship from the
National Foundation for Infantile Paralysis.

J,D, WATSON

F,H,C. CRICK

T e
!i!  Medical Research Council Unit
or the Study of the Molecular Structure
of Biological Systems,
     ~&A
The Cave    Laboratory', Cambridge*


RIEWEREMCES

l*  Pauling, L., and Corey, R.B., Nature, 171, 346 (1953)x Proc,,
              Nat. Aeaa. SC& Wash+ ze, 84 (1953).
2,  Furberg, S,, Acta Chem, Sw.ndr 4, 63& (1952).
3.  Chargaff, El, For references see Zamenhof, S., Brawerman, (3,
      and Chargaff, E., Bioehem* et.Biophys~ Acta, St 402, (1952)
4* Wyatt, CL R*, Jour* Gen. Physu $$ 201, (1952)
59  Astbury, We T., Symosi~m NQ, 1 of the Society for Experimental
           BiolOgY, 66 (1947)*
6e  Wilkins, Me Ha Fe and Randall, & T, Bio~hem et Bio hys. Acta
             30, 192, (1953P.


LEGEI\SD TO F1QUR.E

  This figure is purely diagramatie. The two ribbons aymbolfscs
the two phosphate-sugar Chains, and, the horizontal rods the pairs
of,bases holding the chains together.  The vertical line marks
the fibre axis.

.

.