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  2. Learn about the life and achievements of Erwin Chargaff, a pioneer of DNA research who discovered its base ratios and structure. Find out how he escaped from Austria, Germany and America, and why he was a controversial figure in the field of molecular biology.

    • Overview
    • Introduction
    • The components of DNA
    • Chargaff's rules
    • Watson, Crick, and Rosalind Franklin
    • Watson and Crick's model of DNA
    • Antiparallel orientation
    • Right-handed helix
    • Base pairing
    • The impact of the double helix

    The structure of DNA double helix and how it was discovered. Chargaff, Watson and Crick, and Wilkins and Franklin.

    •A, T, C, and G were not found in equal quantities (as some models at the time would have predicted)

    •The amounts of the bases varied among species, but not between individuals of the same species

    •The amount of A always equalled the amount of T, and the amount of C always equalled the amount of G (A = T and G = C)

    Today, the DNA double helix is probably the most iconic of all biological molecules. It's inspired staircases, decorations, pedestrian bridges (like the one in Singapore, shown below), and more.

    I have to agree with the architects and designers: the double helix is a beautiful structure, one whose form fits its function in a remarkable way. But the double helix was not always part of our cultural lexicon. In fact, until the 1950s, the structure of DNA remained a mystery.

    From the work of biochemist Phoebus Levene and others, scientists in Watson and Crick's time knew that DNA was composed of subunits called nucleotides1‍ . A nucleotide is made up of a sugar (deoxyribose), a phosphate group, and one of four nitrogenous bases: adenine (A), thymine (T), guanine (G) or cytosine (C).

    C and T bases, which have just one ring, are called pyrimidines, while A and G bases, which have two rings, are called purines.

    One other key piece of information related to the structure of DNA came from Austrian biochemist Erwin Chargaff. Chargaff analyzed the DNA of different species, determining its composition of A, T, C, and G bases. He made several key observations:

    •A, T, C, and G were not found in equal quantities (as some models at the time would have predicted)

    •The amounts of the bases varied among species, but not between individuals of the same species

    •The amount of A always equalled the amount of T, and the amount of C always equalled the amount of G (A = T and G = C)

    In the early 1950s, American biologist James Watson and British physicist Francis Crick came up with their famous model of the DNA double helix. They were the first to cross the finish line in this scientific "race," with others such as Linus Pauling (who discovered protein secondary structure) also trying to find the correct model.

    Rather than carrying out new experiments in the lab, Watson and Crick mostly collected and analyzed existing pieces of data, putting them together in new and insightful ways2‍ . Some of their most crucial clues to DNA's structure came from Rosalind Franklin, a chemist working in the lab of physicist Maurice Wilkins.

    Franklin was an expert in a powerful technique for determining the structure of molecules, known as X-ray crystallography. When the crystallized form of a molecule such as DNA is exposed to X-rays, some of the rays are deflected by the atoms in the crystal, forming a diffraction pattern that gives clues about the molecule's structure.

    Franklin’s crystallography gave Watson and Crick important clues to the structure of DNA. Some of these came from the famous “image 51,” a remarkably clear and striking X-ray diffraction image of DNA produced by Franklin and her graduate student. (A modern example of the diffraction pattern produced by DNA is shown above.) To Watson, the X-shaped diffraction pattern of Franklin's image immediately suggested a helical, two-stranded structure for DNA3‍ .

    [Did Watson and Crick steal Franklin's data?]

    Watson and Crick brought together data from a number of researchers (including Franklin, Wilkins, Chargaff, and others) to assemble their celebrated model of the 3D structure of DNA. In 1962, James Watson, Francis Crick, and Maurice Wilkins were awarded the Nobel Prize in Medicine. Unfortunately, by then Franklin had died, and Nobel prizes are not awarded posthumously.

    The structure of DNA, as represented in Watson and Crick's model, is a double-stranded, antiparallel, right-handed helix. The sugar-phosphate backbones of the DNA strands make up the outside of the helix, while the nitrogenous bases are found on the inside and form hydrogen-bonded pairs that hold the DNA strands together.

    In the model below, the orange and red atoms mark the phosphates of the sugar-phosphate backbones, while the blue atoms on the interior of the helix belong to the nitrogenous bases.

    Double-stranded DNA is an antiparallel molecule, meaning that it's composed of two strands that run alongside each other but point in opposite directions. In a double-stranded DNA molecule, the 5' end (phosphate-bearing end) of one strand aligns with the 3' end (hydroxyl-bearing end) of its partner, and vice versa.

    [What is the purpose of the prime marks in 3' and 5'?]

    In Watson and Crick's model, the two strands of DNA twist around each other to form a right-handed helix. All helices have a handedness, which is a property that describes how their grooves are oriented in space.

    [How can I tell that DNA is a right-handed helix?]

    [Are DNA helices always right-handed?]

    The twisting of the DNA double helix and the geometry of the bases creates a wider gap (called the major groove) and a narrower gap (called the minor groove) that run along the length of the molecule, as shown in the figure above. These grooves are important binding sites for proteins that maintain DNA and regulate gene activity.

    In Watson and Crick's model, the two strands of the DNA double helix are held together by hydrogen bonds between nitrogenous bases on opposite strands. Each pair of bases lies flat, forming a "rung" on the ladder of the DNA molecule.

    Base pairs aren't made up of just any combination of bases. Instead, if there is an A found on one strand, it must be paired with a T on the other (and vice versa). Similarly, an G found on one strand must always have a C for a partner on the opposite strand. These A-T and G-C associations are known as complementary base pairs.

    Base pairing explains Chargaff's rules, that is, why the composition of A always equals that of T, and the composition of C equals that of G11‍ . Where there is an A in one strand, there must be a T in the other, and the same is true for G and C. Because a large purine (A or G) is always paired with a small pyrimidine (T or C), the diameter of the helix is uniform, coming in at about 2‍  nanometers.

    Although Watson and Crick's original model proposed that there were two hydrogen bonds between the bases of each pair, we know today that G and C form an additional bond (such that A-T pairs form two hydrogen bonds total, while G-C pairs form three)12‍ .

    The structure of DNA unlocked the door to understanding many aspects of DNA's function, such as how it was copied and how the information it carried was used by the cell to make proteins.

    As we'll see in upcoming articles and videos, Watson and Crick's model ushered in a new era of discovery in molecular biology. The model and the discoveries that it enabled form the foundations for much of today's cutting-edge research in biology and biomedicine.

  3. After Francis Crick, James Watson and Maurice Wilkins received the 1962 Nobel Prize for their work on discovering the double helix of DNA, Chargaff withdrew from his lab and wrote to scientists all over the world about his exclusion.

  4. Jun 20, 2002 · Chargaff's most important contribution to biochemistry was his work with deoxyribonucleic acid, more commonly known as DNA. At the time he was working it was not known that genes were composed of DNA.

  5. His two main discoveries, (i) that in any double-stranded DNA the number of guanine units equals thenumber of cytosine units and the number of adenine units equals the number ofthymine units and (ii) that the composition of DNA varies from one species toanother, are now known as Chargaff's Rules.

    • Nicole Kresge, Robert D. Simoni, Robert L. Hill
    • 2005
  6. Erwin Chargaff was one of the more interesting and colourful figures of the historic decade that heralded the proposal of the double helical structure of DNA by Watson and Crick in 1953. In describing Chargaff's important contribution to the study of DNA, particularly its base composition, this article seeks to suggest why, despite his ...

  7. At first, Chargaff noticed that DNA – whether taken from a plant or animal – contained equal amounts of adenine and thymine and equal amounts of cytosine and guanine. These equalities provided clues into the chemical pairings that make up the double helix.

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