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The Eternal Moleeule

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The Eternal Moleeule 82 50 YEARS OF DNA The eternal moleeule As aprelude to the many celebrations around the world saluting the 50th anniversary of the discovery of the DNA double helix, Nature presents a collection of overviews that celebrate the historical, scientific and cultural impacts of arevelatory molecular structure. ew molecules captivate like DNA. It enthrals minuscule cells of the body, and how an additional Fscientists, inspires artists, and challenges layer of information is encrypted within the proteins society. It is, in every sense, a modern icon. A intimately associated with DNA (page 134). It is per­ defining moment for DNA research was the haps salutary also to recognize what is still to be learnt discovery of its structure half a century ago. On about the physiological states in which DNA exists, as 25 April 1953, in an article in Nature, James Watson discussed by Philip Ball (page 107). and Francis Crick described the entwined embrace of As reviewed by Leroy Hood and David Galas (page two strands of deoxyribonucleic acid. In doing so, 130), DNA science generated the tools that spawned they provided the foundation for understanding the biotechnologyrevolution. Itenabled the cloning of molecular damage and repair, replication and individual genes, the sequencing of whole genomes inheritance of genetic material, and the diversity and and, with the application of computer science, evolution of species. transformed the nature and interactions of molecules The broad influence of the double helix is reflected into an information science. Carlos Bustamante and in this collection of articles. Experts from a diverse co-authors consider how we are stililearning much range of disciplines discuss the impact of the discovery about the distinct structural and physical properties of on biology, culture, and applications ranging from the molecule (page 109). And according to Nadrian medicine to nanotechnology. To help the reader fully Seeman, DNA may develop new applications as a appreciate how far the double helix has travelled, we material for nano sc ale engineering (page 113). also include the original land mark paper by Watson and Crick and the two accompanying papers by Mau­ Influencing society rice Wilkins, who shared the Nobel Prize with Watson Beyond scientific and technological forums, the and Crick in 1962, and by co-discoverer Rosalind double helix has imprinted on society's views of Franklin, and their co-authors (pages 83-87). history, medicine and art. As discussed by Svante Pääbo (page 95), the records of evolution have Transforming science been recalibrated with information traced through Given the immense significance of the double helix, it DNA sequence. On page 98, Aravinda Chakravarti is difficult to imagine a world that wasn't transfixed by and Peter Little revisit the 'nature versus nurture' its discovery. Yet, as Robert Olby recalls on page 88, the debate and our developing view of the interplay proposed structure initially received a lukewarm between genetic and environmental factors in reception. Maclyn McCarty, who, together with human disease. And DNA science will transform Oswald Avery and Colin MacLeod, had previously clinical medicine according to John Bell (page 100), showed DNA to be the substance ofinheritance, shares providing a new taxonomy for human disease and his personal perspective (page 92). triggering a change to health care practice. On In science, where a lifetime's work can often be page 126, Gustav Nossal reviews how an encapsulated in a few shining moments, the greatest understanding of DNA processes, such controversies are sometimes over the sharing of credit. as recombination, have transformed the Heredity The discovery of the double helix is no exception. The field of immunology. premature death and posthumous treatment of As a visual icon, and as a profound I am the family face; Rosalind Franklin, whose X-ray images of DNA influence on our nature, the DNA mole­ Flesh perishes, Ilive on, fibres revealed teIltale clues of a double helical cule has permeated the imagery and art of Projecting trait and trace structure, propelled her portrayal as a feminist icon. our time, and is described by Martin Through time to times anon, But, as discussed here by her biograph er Brenda Kemp (page 102) as the Mona Lisa ofthis And leapingfrom place to place Maddox (page 93), Franklin is better remembered as a scientific age. Given that broad impact, Over oblivion. committed and exacting scientist who saw no bound­ and revolutions that are yet to come, it is aries between everyday life and science. perhaps appropriate to leave the last word The years-heired feature that can Most of our readers will have grown up with the to an artist. Written in 1917, the poem In curve and voice and eye double helix, and yet it is still startling to consider how Heredity by Thomas Hardy (see inset) Despise the human span quickly DNA biology has progressed in just a lifetime. seems to foreshadow both the essence Ofdurance - that is I; Bruce Alberts reviews how the elegant pairing of the and the fascination of the molecule that The eternal thing in man, two strands of the double helix revealed the mecha­ we celebrate here. D That heeds no call to die. nism for replicating the essential units of inheritance (page 117). Errol Friedberg considers the vulnerability Carina Dennis Commissioning Editor Thomas Hardy of the DNA molecule to damage and the multitude of Philip Campbell Editor, Nature (First published in Moments of ways in which cells repair the damage (page 122). And Vision and Miscellaneous Verses, Gary Felsenfeld and Mark Groudine describe how the doi: lO.1038/nature01396 Macmillan, 1917) gargantuan DNA molecule is packaged inside the Original reference: N ature421, 396 (2003). J. Clayton et al. (eds.), 50 Years of DNA © Nature Publishing Group 2003 50 YEARS 0' ONA I 83 No. 4356 April 25, 1953 NATURE 737 equipment, and to Dr. G. E. R. Deacon and the is a re idu on ea.ch chain very 3'4 A. in th z-dire('­ eaptain and offieers of R .R . Di8covery 11 for their tion. We have assunl d an angle of 36° between pa.rt in making the observations. adjacent residue in the same chain, so that th ' Young, F. B., Gerrar<.l, 11., snd Jevons, W., PMl. Mao., 40, 149 structure repeats after 10 residues on ea.ch ehain, that (1920). is, after 34 A. The di tanee of a phosphorus atom I Longuel'Hlgglns, M. ., Jl}'»i. 11'01.. ROll . .d8lro. SO<: .. CeoP"IIB. Stipp., Ii, 285 (1949). from the fibre axis is 10 A. As the phosphates are on I I'on All<, W. ., WOO<!s Hole Papers in Phys. Oceuo!<. Meteor., 11 the outside, cation have easy access to them. (3) (1950). The structure is an open one, and its water eontent ' EkmAn, \', W .. Arkiv.lJfa!. Af/ron. FI/,i.·. (Stocklwlll'). 2 (11) (l1lO1i). is rat her high. At tower water contents we would expect the bases to tilt so that the structure could become more eompact. The novel feature of the structure is the manner MOLECULAR STRUCTU RE OF in wh ich the two chains are held together by the purine and pyrimidine ba.ses. The planes of the ba.ses NUCLEIC ACIDS are perpendieular to the fibre axis. They are joined together in pairs, a single base from one chain being A Structure (or Deoxyribose Nucleic Acid hydrogen-bonded to a single base froro the other E wish to sugg t a strueture for the sa.lt chain, so that the two He side by side with identieal W of deoxyt'ibos nueleie acid (D. .A.). This z-co-ordinates. One of the pair must be a purine and strueture has novel features whieh are of eonsiderable the other 60 pyrimidine for bonding to occur. The biological interest. hydrogen bonds are made as folIows: purine position A strueture for nueleie acid has alrea.dy been 1 to pyrimidine position 1; purine position 6 to propos d by Pauling and Corey'. They kindly mad pyrimidine po ition 6. their manuseript availabl to us in advanee of If it is assumed that the bases on.ly occur in the publieation. Their model consists of three inter­ structure in the most plausible tautomeric forms twined ehains, with the phosphates near the fibre (that is, with the keto rather than the enol con­ axi , and the bases on the outside. In our opinion, figurations) it is found thM only speeific pairs of this structure is unsatisfactory for two reasons: bases can bond together. Th se pairs are: adenin (1) We believe tha the material whieh gives the (purine) with thymine (pyrimidine) and guanine X-ray diagral1l8 is the salt, not the fr acid. Without (purine) with cytosine (pyrimidine). the acidic hydrogen atoms it is not elear what forees In other words, if an adenine forms one member of would hold the structure together, espeeia.l1y as the a pair, on either chain, th n on these assumptions nega ively charged phosphates near the axis will the other member must b thymine; similarly for repel aach other. (2) ome of the van der ' iVaals guanine and eytosine. The sequenee of bases on a. distanees app ar to be too smalI. single chain does not appeal' to be restricted in any Ano her three-ehain structure hag also b en sug­ way. However, if only pecific pairs of bases can be gested by Fraser (in the press). In his model the formed, it follows that if the sequence of bases on phosphate are on th outside and the ba es on the one chain i given, then the sequence on the other inside, linked together by hydrogen bonds. 'fhis ehain is automatically determined.
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