Watson and Crick Model of DNA

12 Key excerpts on "Watson and Crick Model of DNA"

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  Introduction to Bioorganic Chemistry and Chemical Biology

  • David Van Vranken, Gregory A. Weiss(Authors)
  • 2018(Publication Date)
  • Garland Science

    (Publisher)

  The frenetic race to solve this puzzle, arguably the most important structural problem in the field of natural products, is now the stuff of history. In 1953, using Rosalind Franklin’s highly accurate X-ray diffraction data, James D. Watson and Francis Crick published a correct interpretation of the struc- ture of DNA—a complementary double helix held together by hydrogen bonds (Figure 3.1). Their dryly written paper ends with an incandescent understatement: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Indeed, the comple- mentary double-helical model of Watson and Crick provides a chemical basis for the storage of genetic information, for replication, and for mutation—key requirements for evolution (Figure 3.2). All known examples of evolution, either found in Nature or developed in the laboratory, are based on the Watson–Crick paradigm. Of course, the importance of DNA transcends the ability to store information faithfully. DNA holds a unique position at the headwaters of biomolecular synthesis, and thus it controls all chemistry within living cells. This chapter is devoted to the chemistry of DNA, not at the level of molecular biology but at the deeper chemical level of atoms and bonds. 3.1 FoRms oF DNA The canonical double helix is one of several forms of DNA Double-stranded nucleic acids generally adopt one of three types of helical conforma- tions, namely A, B, or Z. The A form is shorter and fatter and is usually found in RNA/ RNA or DNA/RNA duplexes. The B form is the canonical conformation proposed by Figure 3.1 The Watson–Crick model for DNA. the double-helix model was revolutionary, consisting of complementary strands rather than identical strands. the double helix is now an icon for molecular biology. the drawing of DNA on the left is from the seminal Watson and Crick paper first reporting the double-helix structure of DNA.

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  Nobel Prizes That Changed Medicine

  • Gilbert R Thompson(Author)
  • 2011(Publication Date)
  • ICP

    (Publisher)

  Pauling sent a copy of his manuscript to his son, Peter, who was working in Cambridge at that time and the latter showed it to Watson and Crick. Pauling’s proposed model was a three-chain helix with its phosphate groups on the inside. 14 However, the phosphates in Pauling’s model were un-ionised, which Watson and Crick immediately perceived to be a major flaw in the model and Pauling later admitted his mistake. 12 The Discovery of the Structure of DNA 97 5.4.3 The correct model After Wilkins showed Franklin’s X-ray diffraction photograph of the B form of DNA to Watson, which the latter immediately interpreted as indicative of a helical structure (Fig. 5.2), the question remained as to how many helices comprised each DNA molecule. Existing data regarding the density of its sodium salt suggested there were not less than two and not more than three helices and Watson opted for two, basing his assumption on the premise that, ‘important biological objects come in pairs’. 2 The next question needing to be resolved was the location of the sugar–phosphate backbone in each helix. Franklin’s data suggested that the phosphate groups were exposed and therefore on the outside of the helix whereas Watson and Crick’s initial model had the back-bone inside and the purine and pyridimine bases on the outside. However, their model looked ‘awful’, and they soon came to the conclusion that the bases probably formed the core and the sugar–phosphate backbone the circumference of the helix. 15 Early in 1953 Max Perutz showed Crick the report which Randall’s group had produced for the MRC Biophysics Research Committee. This contained unpublished calculations by Franklin which enabled Crick to deduce that the helices in DNA were anti-parallel, i.e. they 98 J. Scott and G. Thompson Fig. 5.2. X-ray diffraction patterns of the A and B forms of the sodium salt of DNA obtained by RE Franklin and RG Gosling in 1953.

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  Understanding DNA

  The Molecule and How it Works

  • Chris R. Calladine, Horace Drew, Ben Luisi, Andrew Travers(Authors)
  • 2004(Publication Date)
  • Academic Press

    (Publisher)

  All parts of the DNA sugar– phosphate chain are rigid locally, but they have this kind of indirect rotational flexibility over several bonds. We have almost finished our survey of the basic principles that determine the structure of DNA. All we have to do now is to learn how the bases adhere to one another in the central core of the double helix. James Watson and Francis Crick solved this problem in 1953, by putting forward a set of rules for base-pairing. They said that the most stable base pairs would be of the kind A–T or G–C, as shown in Fig. 2.11(a) and (b). One advantage of their scheme was that all four possible Watson–Crick base pairs, A–T, T–A, G–C, and C–G, were of the same size, and hence could fit easily into the framework of a reg-ular double helix. Another advantage was that it explained how the genes in DNA could be duplicated (or stably inherited) on cell divi-sion. Whenever a cell divides, and needs to duplicate its DNA, it can do so simply by splitting the DNA into two separate strands; then certain enzymes will come along and use each of these old strands as a ‘template’ for the precise synthesis of a new strand, according to the Watson–Crick rules of base pairing: A with T and G with C. (More will be said about this in Chapter 4.) Note that some of the interatomic connections within the A, T, G, and C rings are drawn as two lines, rather than as one: these are the ‘double bonds’, which give the base rings both their flatness and their rigidity. Also note that the CH 3 or methyl group on the 30 Understanding DNA thymine ring would be absent in RNA, where the methyl-less base is called ‘uracil’ (see the right-hand part of Fig. 2.13 and its caption).

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  Fundamentals of Natural Computing

  Basic Concepts, Algorithms, and Applications

  • Leandro Nunes de Castro(Author)
  • 2006(Publication Date)
  • Chapman and Hall/CRC

    (Publisher)

  As for symbols on a string, there is no restriction on nucleotides in the sequence. However, the bonds between the bases can only occur by the pair-wise attraction of the following bases: A binds with T, and G binds with C. This is called the Watson-Crick complementarity , after J. D. Watson and F. H. C. Crick who discovered the double helix structure of DNA. Basic Concepts from Molecular Biology 454 5 ′ 4 ′ 3 ′ 2 ′ 1 ′ Base P 5 ′ 4 ′ 3 ′ 2 ′ 1 ′ Base P 5 ′ 4 ′ 3 ′ 2 ′ 1 ′ Base P Base 1 ′ 2 ′ 3 ′ 4 ′ 5 ′ P 5 ′ 4 ′ 3 ′ 2 ′ 1 ′ Base P (a) (b) Figure 9.3: The two types of bonding between nucleotides: (a) covalent or phosphodi-ester bond; and (b) hydrogen bond, which has to obey the Watson-Crick complementarity (A-T and C-G). Since DNA consists of two complementary strands bond together, these units are often called base pairs . The length of a DNA sequence is often measured in thousands of bases, abbreviated kb. Nucleotides are generally abbreviated by their first letter, and appended into sequences, written, e.g., GTACAGTT. The nucleotides are linked to each other in the polymer by phosphodiester bonds. It can be observed from Figure 9.3, that the bond is directional; a strand of DNA has a head (the 5 ′ end) and a tail (the 3 ′ end). One well known fact about DNA is that it forms a double helix; that is, two helical (spiral-shaped) strands of the polypeptide, running in opposite directions, held together by hydrogen bonds (Figure 9.4). C T G A G A C T 5 ′ 3 ′ 5 ′ 3 ′ (a) DNA Computing 455 A T C G A T C G T A G C T A G C (b) Figure 9.4: Other representations of the DNA molecule. (a) A schematic representation of a DNA molecule depicting the sugar-phosphate backbone, the complementary bonding between bases forming the base pairs, and the directional bonding. (b) The double helix of DNA. A is complementary to T, and C is complementary to G. The single stranded sequences of nucleotides have a directionality given by the carbons used by the covalent bonds.

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  Molecular Biophysics

  • M Volkenstein(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  The specific reversible conformational transition of DNA that is thus established may have some biological significance. 8 . 3 Intramolecular Interactions in the Double Helix According to the original suggestion, the double-helical structure of DNA is due to hydrogen bonds fixing the Watson-Crick pairs (Fig. 8.5). The determining role of three hydrogen bonds in G-C and of two hydrogen bonds in A-T seem to be quite natural. This suggestion agrees with the results of X-ray analysis. However, actual determination of the nature of the interactions in the double helix requires special theoretical and experimental investigation. The quantitative data charac-terizing these interactions can be obtained by quantum-mechani-cal calculations and physical studies of simple monomeric models. Free nitrogen bases form the hydrogen-bonded purine-pyrim-idine complexes in the solid state. This was first estab-lished by Hoogsteen [50], who obtained such a complex by means of the common crystallization of 9-methyladenine with 1-methyl-thymine (MA-MT) . The Ν χ atom in Τ and N g atom in A were blocked by the methyl groups, preventing the formation of additional hydrogen bonds. X-ray analysis of the MA-MT crystal showed that the structure of the complex differs from the Watson-Crick structure (WCS) (Fig. 8.13; cf. Fig. 8.5). The Ni atom in MT forms a hydrogen bond not with MA but with the imidazole N7. A similar Hoogsteen structure (HS) was established for the com-plex formed by 9-ethyladenine with 1-methyluracil (EA-MU) [51]. It is possible that the HS is more stable than the WCS already in the solution. Another possibility is that the type of com-plex occurring in the crystal is determined by the crystalline packing. Infrared and NMR spectroscopy of solutions show that purine-pyrimidine complexes actually are formed, but these tech-niques do not enable us to determine the complexes' structure [52-57].

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  DNA Replication

  Current Advances

  • Herve Seligmann(Author)
  • 2011(Publication Date)
  • IntechOpen

    (Publisher)

  8. It is time to make a conceptual change In the history of discovery, similar stories incredibly repeated again and again. The garden pea experiment of Mendel was ignored by his contemporary scientists for 35 years; proteins were assumed to be the carriers of heredity for a very long period of time; the long stories in discovering Krebs cycle, transposon, prion, ribozyme happened in different scenarios (Grinnell, 2011). Almost all of these cases occurred due to an analogous reason — old minds die hard. The prevalently accepted dogma is always believed to be true and correct, and the new concept is believed to be bizarre and weird. The famous notion of “chance favors the prepared mind” is routinely displayed in an alternative way: “novel new concept is always being neglected, rejected or even hated by unprepared mind”. The basic idea of the Watson - Crick Model is correct and was proved by numerous experimental findings afterwards. Its contribution to molecular biology is highly evaluated. However, in native DNA, the winding direction of the two strands inside the double helix is very difficult to detect. Available evidence is scarce, obscure and questionable. The only source comes from the x-ray analysis of DNA fiber, which could not rule out the presence of left-handed DNA. Currently, most people take the double helix as a scientific doctrine, but in 1953 it was merely an untested hypothesis as Watson and Crick recognized themselves. Even in a textbook of 1958, the double helix model was described as “an ingenious speculation”. (Fruton & Simmonds, 1958) Epistemology tells us that no theory is perfect. Even a theory as sound as Newtonian physics, is not unassailable. No matter how a theory survived the most rigorous tests, it does not mean it can pass all future tests.

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  Fundamentals of Biochemistry, Integrated E-Text with E-Student Companion

  Life at the Molecular Level

  • Donald Voet, Judith G. Voet, Charlotte W. Pratt(Authors)
  • 2017(Publication Date)
  • Wiley

    (Publisher)

  Further analysis suggested that the hydrophilic sugar–phosphate chains were on the outside of the helix and the relatively hydrophobic bases were on the inside. However, although Franklin was aware of Chargaff’s rules (Section 3-2A) and Jerry Donohue’s work concerning the tautomeric forms of the bases (Section 3-2B), she did not deduce the existence of base pairs in double-stranded DNA. In January 1953, Wilkins showed Franklin’s X-ray photograph of B-DNA to Watson, when he visited King’s College. Moreover, in February 1953, Max Perutz (Box 7-2), Crick’s thesis advisor at Cambridge University, showed Watson and Crick his copy of the 1952 Report of the MRC, which summarized the work of all of its principal investigators, including that of Franklin. Within a week (and after 13 months of inactivity on the project), Watson and Crick began building a model of DNA with a backbone structure compatible with Franklin’s data [in earlier modeling attempts, they had placed the bases on the outside of the helix (as did a model published by Linus Pauling; Box 6-1) because they assumed that the bases could transmit genetic information only if they were externally accessible]. On several occasions Crick acknowledged that Franklin’s findings were crucial to this enterprise. Watson and Crick published their model of B-DNA in Nature in April 1953. The paper was followed, back-to-back, by papers by Wilkins and by Franklin on their structural studies of DNA. Franklin’s manuscript had been written in March 1953, before she knew about Watson and Crick’s work. The only change that Franklin made to her manuscript when she became aware of Watson and Crick’s model was the addition of a single sentence, “Thus our general ideas are not inconsistent with the model proposed by Watson and Crick in the preceding communication.” She was apparently unaware that the Watson–Crick model was, to a significant extent, based on her work

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  Pharmaceutical Chemistry E-Book

  • David G. Watson(Author)
  • 2011(Publication Date)
  • Churchill Livingstone

    (Publisher)

  Chapter 7 DNA structure and its importance to drug action

  Simon P. Mackay

  Chapter contents

  Introduction 131

  The structural components of DNA – DNA primary structure 132

  DNA bases 132

  Pyrimidine bases 132

  Purine bases 133

  Deoxynucleosides 133

  Deoxynucleotides 133

  Complementary hydrogen bonding between DNA strands 134

  DNA secondary structure – the double helix 138

  Conformation of the deoxyribose sugar 138

  Conformation of the base with respect to the sugar 138

  The phosphodiester bonds 139

  Base pair stacking 139

  Why a helix, not a ladder? 140

  Helical grooves – major and minor 140

  Helical repeat/pitch 141

  A-DNA 141

  RNA 142

  Nucleic acid processing 143

  Nucleic acid processing enzyme targets for drug action 144

  The origins of torsional strain in DNA 145

  Introduction

  The elucidation of the structure of deoxyribonucleic acid (DNA) in 1953 by James Watson and Frances Crick was one of the major scientific events of the last century. The recent unravelling of the human genome would not have been possible today without Watson and Crick’s fundamental descriptions of the role of complementary base pairing and the organisation of the component deoxynucleotides into a double helical structure. Since Rosalind Franklin’s groundbreaking research using X-ray crystallography to define two general forms of helical DNA, a whole variety of experimental techniques have shown that the structure of DNA is far more complex than originally proposed. Not only are there different morphological states (e.g. A, B, Z), the structure is also sequence dependent, where the order of the nucleotides can influence the three-dimensional shape in different regions of the helix. Such variations in structure according to sequence are fundamental to the function of DNA and its interactions with the many different proteins that seek to influence its role in cellular biochemistry. It is not the purpose of this chapter to discuss in depth the minutiae of DNA structural variations; there is already a wealth of literature available which describes these phenomena. Here, we provide the basics of DNA structure and function in order to lay foundations for later chapters where DNA plays a part in the pharmacological action of specific drugs. These work through a variety of chemical mechanisms including DNA cleavage and cross-linking, or by reversible association, usually by intercalation or binding in one of the DNA grooves. It is fair to say that a number of drugs whose cellular target is DNA were in use before the structure of DNA had been solved, or even before it was recognised as the repository of the genetic code, e.g.

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  Mathematics of Bioinformatics

  Theory, Methods and Applications

  • Matthew He, Sergey Petoukhov, Yi Pan, Albert Y. Zomaya(Authors)
  • 2011(Publication Date)
  • Wiley-Interscience

    (Publisher)

  Mathematics can be used to model these complicated processes. In this chapter we provide an introduction to the structures of DNA; key elements of knot theory, such as links, tangles, and knot polynomials; and applications of knot theory to the study of closed circular DNA. The physical and chemical properties of this type of DNA can be explained in terms of basic characteristics of the linking number, which is invariant under continuous deformation of the DNA structure and is the sum of two geometric quantities, twist and writhing. This chapter is in no way exhaustive of all the topological applications in DNA structures. For comprehensive coverage of the topology of DNA, readers should consult the excellent survey articles in the field (e.g., Sumners, 1987, 1990, 1992).

  4.1 INTRODUCTION

  DNA is a double-stranded molecule composed of two polarized strands (of deoxyribonucleotide polymers) which run in opposite directions (termed antiparallel ) and wind around a central, common axis. One is entwined about the other such that an overall helical shape results (known as a plectonemic helix ). Both are wound in a right-handed manner. This structure is to be contrasted with a paranemic helix , in which a pair of coils lie side by side without interwinding. The strands are occasionally distinguished as the Watson strand and the Crick strand.

  In the case of the molecular structure of eukaryotic chromosomes in each human cell, two meztres of DNA is packaged into the cell nucleus. To access the information, the DNA must be unwound as a double helix and needs to be “spread out” in the nucleus. However, during cell division (mitosis), in order to move the strands around, they are packaged into dense bundles as follows :

  • Nucleosome formation (beads on a string): 2.5 loops of DNA wrapped around core DNA
  • Solenoid formation (beaded string is coiled): six nucleosomes per solenoid coil
  • Supercoiling (coil of solenoids is itself coiled): the coiled coil is then folded, as in a mitotic chromosome (i.e., a 10,000-fold reduction in length)

  Each nucleotide base of one strand is paired with a nucleotide base on the other strand to create a stable structure of the two polymers. The pairing of the four types of bases (A, T, C, G) by hydrogen bonds is not random: An A pairs with a T and a G pairs with a C. The bases on the outside of the helix are exposed to solvent within two grooves along the helix, the major groove and the minor groove. It is within these grooves that DNA interacts with other molecules. The three structural variations of these grooves (A, B and Z DNA), which differ in the relationship between the bases and the helical axis, offer one mechanism by which reactivity of DNA is modulated:

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  Understanding Cancer

  • Robin Hesketh(Author)
  • 2022(Publication Date)
  • Cambridge University Press

    (Publisher)

  A phosphate group is made up of one phosphorus and four oxygen atoms. Sugars are sweet-tasting carbohydrates with the general for- mula C n (H 2 O) n . Table sugar is sucrose (fructose + glucose). DNA was shown to be the material that chromosomes and genes are made from by the Canadian Oswald Avery and co-workers in 1944. In 1952 Alfred Hershey and Martha Chase confirmed DNA to be the carrier of genetic information by showing that viruses that infect bacteria (bacteriophages) do so by injecting their DNA into the recipient cell. Hershey went on to share FROM DNA TO PROTEIN 49 a Nobel Prize with Max Delbrück and Salvador Luria for their work on the structure of viruses. Avery didn’t get a Nobel Prize – but he does have a crater on the moon named in his honour. How DNA is put together is, of course, important but the only thing that really matters is that the sequence of bases carries the genetic information that instructs cells to make proteins by gluing small building blocks (amino acids) together into huge chains. Everything does indeed stem from DNA, although it makes up only 0.25 per cent of the mass of a cell. How does that work? The Double Helix It’s widely known that DNA in cells forms a double helix, and almost as well known that two chaps, James Watson and Francis Crick, worked this out in Cambridge in 1953. They built their celebrated model using X-ray crystallog- raphy data acquired by Rosalind Franklin and Maurice Wilkins at King’s College London. For the structure to be stable, Watson and Crick concluded that the bases in one chain poke into the middle of the double helix (a little bit like the treads on a spiral staircase) and these pair, in a weak interaction, with bases on the opposite chain (Figure 4.1). The weak interaction is a hydrogen bond. Much weaker than covalent bonds, hydrogen bonds create the liquid state of water because the hydrogen atoms of one water molecule are attracted to the oxygen atom of a nearby molecule.

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  Language and Social Cognition

  Expression of the Social Mind

  • Hanna Pishwa(Author)
  • 2009(Publication Date)
  • De Gruyter Mouton

    (Publisher)

  Chapter 11 Distributed cognition and play in the quest for the double helix L. David Ritchie 1. Introduction I have never seen Francis Crick in a modest mood . Perhaps in other company he is that way, but I have never had reason so to judge him . It has nothing to do with his present fame . Already he is much talked about, usually with reverence, and some-day he may be considered in the category of Rutherford or Bohr . But this was not true when, in the fall of 1951, I came to the Cavendish Laboratory of Cambridge University to join a small group of physicists and chemists working on the three-dimensional structures of proteins (Watson 1968: 16) . The discovery of the double helix structure of the DNA molecule is a prime example of both extended cognition (Clark 1997) and distributed cognition (Hutchins 1995) . In large part due to the refreshingly candid (inappropriately candid according to some critics) autobiographical reminiscences of James Watson (1968), one of the discoverers, it also provides an unusual insight into the social and emotional experience of science . Watson’s account stimulated several others to write their own accounts, the cumulative result of which is a fascinating study in the retrospective reconstruction of culturally significant events . In his controversial account of the events leading up to the discovery, Watson shuns the more conventionally heroic reconstruction of a great discovery as an orderly process of reasoning from known facts to new observations, then to logi-cal conclusions . Watson chooses instead to focus on the “very human events in which personalities and cultural traditions play major roles,” and to “convey the spirit of an adventure characterized both by youthful arrogance and by the belief that the truth, once found, would be simple as well as pretty” (p . ix) .

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  Biophysics of DNA

  • Alexander Vologodskii(Author)
  • 2015(Publication Date)
  • Cambridge University Press

    (Publisher)

  This difference in the number of hydrogen bonds is responsible for a higher thermal stability of GC base pairs (although base pairing per se does not stabilize the double helix (Yakovchuk et al. 2006)). The base pairs do not just have very close dimensions, but also their external geometries related to the backbones are nearly identical and have an important pseudosymmetry. The bonds between the nitrogens of the bases and C 1  atoms of the sugar rings form the same angle of 51.5° with the C 1  –C 1  line for all four bases of AT and GC base pairs (see Fig. 1.4). Base-pair geometry specifies the distance between C 1  atoms across the pair, and this distance is exactly the same for both AT and GC pairs. Therefore, in either of two orientations (AT or TA, and GC or CG) the base pairs can be very well incorporated in a uniform helical structure of the backbones. It is this pseudosymmetry that makes Watson–Crick base pairing so unique. Many other possible patterns of base pairing do not have this symmetry and cannot be incorporated into a uniform structure of the backbones. 1.2.1 B-DNA B-DNA, a form that the double helix has in aqueous solutions, is a right-handed helix with a helical period close to 10.5 bp per turn (Wang 1979, Peck & Wang 1981, Goulet et al. 1987). Its external diameter is approximately 2.0 nm (Dickerson & Ng 2001). The complementary strands have antiparallel orientations. The base pairs are located inside the helix, while the backbones are at the helix exterior (Fig. 1.5). The helix has two dyad symmetry axes that are perpendicular to the helix axis (assuming that the helix ends are extended to infinity). One of them passes through the plane of the bases (see Fig. 1.4). The other one passes between two base pairs. These are true symmetry axes for the backbone and pseudosymmetry axes for the base pairs. For Double helices 5 Figure 1.4 Complementary base pairs of DNA.

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