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Nucleic acids were found in 1869 by Miescher, who called them nuclein. Later, scientists showed they were made of bases and sugar–phosphate. At first, people thought proteins carried genes, but experiments by Avery and Hershey–Chase proved DNA was the genetic material. In 1953, Watson and Crick, using Rosalind Franklin’s data, discovered DNA’s double-helix shape.
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In the early 1900s, Phoebus Levene studied DNA and discovered its basic parts. He showed that DNA is made of units called nucleotides, and each nucleotide has three components: a sugar, a phosphate group, and one of four bases (A, T, C, or G). Levene thought DNA was too simple to be the genetic material, but his discovery of nucleotides was a key step in understanding how DNA works and how it stores information.
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The tetranucleotide hypothesis of Levene proposed that DNA was composed of repeating sequences of four nucleotides. It was very influential for three decades, and the diagram at the right illustrates the view of Levene and Tipson. In 1940, at the time of Levene's death, Bass wrote in his obituary As a result of Levene’s work we have an exact concept of the structures of these huge molecules, probably the most complex biological materials whose architectural picture has been reconstructed.
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Frederick Griffith did experiments with two types of bacteria that cause pneumonia: one harmless and one deadly. He found that when he killed the deadly bacteria and mixed them with the harmless ones, the harmless bacteria became deadly too. He called this the “transforming principle.” Griffith didn’t know it yet, but what was being transferred was DNA, the genetic material.
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Oswald Avery, Colin MacLeod, and Maclyn McCarty continued Griffith’s work. They wanted to know what the “transforming principle” was. By carefully destroying proteins, lipids, and RNA, they found that only when DNA was destroyed, the transformation stopped. This proved that DNA is the molecule that carries genetic information, not proteins, as many scientists had believed before.
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Linus Pauling, who discovered the structure of the alpha helixes and the beta sheets in proteins, he came up with a triple helix model, again, with the phosphates and the sugar on the inside and the nucleobases on the outside. He was more certainly looking at x-ray crystallography images that were mixtures from both the A and the B form.
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The race was on to determine the structure of DNA in cells and to determine how it codes for proteins and how it replicates.
The problem: DNA exist in two forms: A form (dry form), B form (wet form, as DNA exists in cells) In 1951, Watson and Crick wrote a paper in which they described DNA as a double helix with sugars and phosphate at the centre ant the nucleobases facing the outside. This model was quickly shown to be incorrect and in fact it made no chemical sense -
Alfred Hershey and Martha Chase used viruses that infect bacteria (bacteriophages) to find out what carried genetic information. They labeled the virus’s DNA with radioactive phosphorus and its protein coat with radioactive sulphur. When the viruses infected bacteria, only the DNA entered the cells, not the proteins. This proved that DNA, not protein, is the genetic material.
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DNA is made of four bases: adenine (A), thymine (T), cytosine (C), and guanine (G). A scientist named Erwin Chargaff studied DNA in the 1940s and 1950s and discovered something important: the amount of A always equals T, and the amount of C always equals G. This is called Chargaff’s rules. His discovery helped scientists understand how bases pair up inside the DNA double helix.