The DNA double helix fifty years on

Proceedings of the National Academy of Sciences, 1978

We have constructed a space-filling (Corey-Pauling-Koltun) model of an alternative structure for DNA. This structure is not a double helix, but consists of a pair of polynucleotide strands lying side by side and held together by Watson-Crick base pairing. Each of the two strands has alternating right- and left-handed helical segments approximately five base pairs in length. Sugar residues in alternating segments along a strand point in opposite directions. A structure slightly different from the present one proposed earlier by ourselves and another group and in which sugars in a strand all point in the same direction is ruled out. The present structure yields natural solutions to the problems of supercoiling of DNA and of strand separation during DNA replication. This model is energetically more favorable than the double helix.

Alternative model of DNA double helix

Commonly accepted model of DNA double helix is made from two right handed strands wound around each other. This model has problems with assembly and dissociation. We propose another form of double helix which seems to be better suitable for the purpose. It works like coil zipper lock, and can assemble from individual strands and separate without the problems of the standard model. It would be desirable to re-evaluate existing data used to confirm accepted structure in regard to see how they fit to the zip-lock model.

2018

The well-known difficulty of the Watson-Crick model gives the right to assume its incorrectness. An alternative model of the structure of the DNA molecule called a ribbon helix is proposed. Unlike the double helix, in it two chains are not intertwined, but go in parallel; unlike another earlier proposed structure, the so-called side-by-side model, it differs in that it has a homogeneous, dextrorotatory character. The advantages of the proposed structure are shown.

Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences, 2011

Famously, James Watson credited the discovery of the double-helical structure of DNA in 1953 to an X-ray diffraction photograph taken by Rosalind Franklin. Historians of molecular biology have long puzzled over a remarkably similar photograph taken two years earlier by the physicist and pioneer of protein structure William T. Astbury. They have suggested that Astbury's failure to capitalize on the photograph to solve DNA's structure was due either to his being too much of a physicist, with too little interest in or knowledge of biology, or to his being misled by an erroneous theoretical model of the gene. Drawing on previously unpublished archival sources, this paper offers a new analysis of Astbury's relationship to the problem of DNA's structure, emphasizing a previously overlooked element in Astbury's thinking: his concept of biological specificity.

Journal of the American Chemical Society, 2018

According to the iconic model, the Watson-Crick double helix exploits nucleobase pairs that are both size complementary (big purines pair with small pyrimidines) and hydrogen bond complementary (hydrogen bond donors pair with hydrogen bond acceptors). Using a synthetic biology strategy, we report here the discovery of two new DNA-like systems that appear to support molecular recognition with the same proficiency as standard Watson-Crick DNA. However, these both violate size complementarity (big pairs with small), retaining hydrogen bond complementarity (donors pair with acceptors) as their only specificity principle. They exclude mismatches as well as standard Watson-Crick DNA excludes mismatches. In crystal structures, these "skinny" and "fat" systems form the expected hydrogen bonds, while conferring novel minor groove properties to the resultant duplex regions of the DNA oligonucleotides. Further, computational tools, previously tested primarily on natural DNA...

Biochemistry, 1988

Conformational analysis of D N A shows that the origin of the B-form double helix can be attributed in large part to the atomic charge pattern in the base pairs. The charge patterns favor specific 'Research sponsored, at least in part, by the NCI, DHHS, under 'National Cancer Institute. 5 NCI-Frederick Cancer Research Facility.

Biochemistry, 1991

Raman spectra of the parallel-stranded duplex formed from the deoxyoligonucleotides 5'-d-[(A),,TAATTTTAAATATTT]-3' (Dl) and 5'-d[(T),,,ATTAAAATTTATAAA]-3' (D2) in H 2 0 and D 2 0 have been acquired. The spectra of the parallel-stranded DNA are then compared to the spectra of the antiparallel double helix formed from the deoxyoligonucleotides D1 and 5'-d(AAATATTTAAAATTA-(T),,]-3' (D3). The Raman spectra of the antiparallel-stranded (aps) duplex are reminiscent of the spectra of poly[d(A)].poly[d(T)] and a B-form structure similar to that adopted by the homopolymer duplex is assigned to the antiparallel double helix. The spectra of the parallel-stranded (ps) and antiparallel-stranded duplexes differ significantly due to changes in helical organization, i.e., base pairing, base stacking, and backbone conformation. Large changes observed in the carbonyl stretching region (1600-1700 cm-') implicate the involvement of the C(2) carbonyl of thymine in base pairing. The interaction of adenine with the C(2) carbonyl of thymine is consistent with formation of reverse Watson-Crick base pairing in parallel-stranded DNA. Phosphate-furanose vibrations similar to those observed for B-form DNA of heterogenous sequence and high A,T content are observed at 843 and 1092 cm-' in the spectra of the parallel-stranded duplex. The 843-cm-' band is due to the presence of a sizable population of furanose rings in the C2'-endo conformation. Significant changes observed in the regions from 1150 to 1250 cm-' and from 1340 to 1400 cm-' in the spectra of the parallel-stranded duplex are attributed to variations in backbone torsional and

Inference: International Review of Science, 2021

In Unravelling the Double Helix: The Lost Heroes of DNA, Gareth Williams traces the stories of scientists from the mid-nineteenth century onward as they were, in one way or another, involved in research on DNA and “were variously enthralled, seduced or infuriated” by it. Some of the lesser known of these stories include the discoveries of DNA and of its function as the carrier of life’s instructions.

Chemical Communications, 2011

L-DNA, the mirror image of natural DNA forms structures of opposite chirality. We demonstrate here that a short guanine rich L-DNA strand forms a tetramolecular quadruplex with the same properties as a D-DNA strand of identical sequence, besides an inverted circular dichroism spectra. L-and D-strands self exclude when mixed together, showing that the controlled parallel self-assembly of different G-rich strands can be obtained through L-DNA use.

It is generally assumed that DNA structure has been solved by Watson-Crick in 1953. However, the finding of zero linking number topoisomer indicated that the winding direction inside the double helix should be ambidextrous, rather than plectonemic. Hence, a double helix conjecture was proposed that in any kind of plasmid a zero linking number topoisomer, i.e., a non-linked plasmid，could be found. By denaturing and renaturing plasmid in various different ways, the topological transformation of the DNA was observed by agarose gel electrophoresis. We found that the two strands of a covalently closed circular DNA molecule can be completely dissociated under very mild conditions and this dissociation is reversible. The experimental phenomena indicated that two strands of DNA are unlikely winding right-handedly as in the canonical double helix model. It paves the way for the demonstration of the double helix conjecture which would provide solid evidence to amend the Watson-Crick Model. Abbreviations: DNA I, super coiled DNA; DNA II, nicked DNA; DNA III, linear DNA; DNA IV, denatured DNA; ssc DNA, single stranded circular DNA; ssl DNA, single stranded linear DNA; EthBr, ethidium bromide.

Journal of the American Chemical Society, 2006

We describe the NMR-derived solution structure of the double helical form of a designed 8-base genetic pairing system, termed xDNA. The benzo-homologous xDNA design contains base pairs that are wider than natural DNA pairs by ca. 2.4 Å (the width of a benzene ring). The eight component bases of this xDNA helix are A, C, G, T, xA, xT, xC, and xG. The structure was solved in aqueous buffer using 1D and 2D NMR methods combined with restrained molecular dynamics. The data show that the decamer duplex is right-handed and antiparallel, and hydrogen-bonded in the analogous way as Watson-Crick DNA. The sugar-phosphate backbone adopts a regular conformation similar to that of B-form DNA, with small dihedral adjustments due to the larger circumference of the helix. The grooves are much wider and more shallow than those of B-form DNA, and the helix turn is slower, with ca. 12 base pairs per 360° turn. There is extensive intra-and inter-strand base stacking surface area, providing an explanation for the greater stability of xDNA relative to natural DNA. There is also evidence for greater motion in this structure compared to a previous two-base expanded helix; possible chemical and structural reasons for this are discussed. The results confirm paired selfassembly of the designed xDNA system. This suggests the possibility that other genetic system structures besides the natural one might be functional in encoding information and transferring it to new complementary strands.

Handbook of Nanomaterials Properties, 2014

Philosophy of Photography, 2013

is a photographer and documentary filmmaker, author of numerous documentaries and photographic exhibitions. He has published articles and books related to his main subject of investigation: the role played by photography in the acquisition of scientific knowledge. Personal and academic interests are focused on the study of the relationship between art and science through the theory and practice of photography. His most recent book is Photography and Knowledge: Photography in the Age of Electronics: From its Origins to 1975

Biopolymers, 2013

The coding sequences for genes, and much other regulatory information involved in genome expression, are located 'inside' the DNA duplex. Thus the 'macromolecular machines' that readout this information from the base sequence of the DNA must somehow access the DNA 'interior'. Double-stranded (ds) DNA is a highly structured and cooperatively stabilized system at physiological temperatures, but is also only marginally stable and undergoes a cooperative 'melting phase transition' at temperatures not far above physiological. Furthermore, due to its length and heterogeneous sequence, with AT-rich segments being less stable than GC-rich segments, the DNA genome 'melts' in a multistate fashion. Therefore the DNA genome must also manifest thermally driven structural ('breathing') fluctuations at physiological temperatures that should reflect the heterogeneity of the dsDNA stability near the melting temperature. Thus many of the breathing fluctuations of dsDNA are likely also to be sequence dependent, and could well contain information that should be 'readable' and useable by regulatory proteins and protein complexes in site-specific binding reactions involving dsDNA 'opening'. Our laboratory has been involved in studying the breathing fluctuations of duplex DNA for about 50 years. In this 'Reflections' article we present a relatively chronological overview of these studies, starting with the use of simple chemical probes (such as hydrogen exchange, formaldehyde and simple DNA 'melting' proteins) to examine the local stability of the dsDNA structure, and culminating in sophisticated spectroscopic approaches that can be used to monitor the breathing-dependent interactions of regulatory complexes with their duplex DNA targets in 'real time'.