The History of DNA

Early Work Friedrich Miescher, 1869, first isolates a substance from the nucleus of cells that he calls “nuclein.” His student, Richard Altmann, calls the substance “nucleic acid.” Biochemists identify two types of nucleic acids, later called RNA and DNA. In 1929, Phoebus Levine at the Rockefeller center identifies the four bases of DNA.

What Does DNA Do? Though early researchers knew that DNA was found in chromosomes, they doubted that it was the hereditary material. There were only four bases. How could for bases code for all sorts of proteins? Some researchers, including Linus Pauling, thought that the protein also found in chromosomes was probably the hereditary factor.

Frederick Griffith In 1928, Frederick Griffith carried out experiments on pneumonia bacteria in mice. Discovery: something in heat-killed virulent bacteria could be transferred to live, harmless bacteria and make them virulent.

Griffith’s Experiment

Oswald Avery Avery continued working with Griffith’s findings in hope of discovering what factor in bacteria carried the trait of virulence. Isolated proteins, carbohydrates, nucleic acids and applied them to non-virulent bacteria. Only nucleic acids (DNA) caused a change.

Avery’s Work

Avery, Mcleod and McCarty Continued with Griffith’s experiment and characterized the “transforming principle” first described by Griffith.

Erwin Chargaff Chargaff studied DNA itself, in hopes of providing some clues about its structure. Discovered that there are always equal amounts of the bases Adenine and Thymine, and equal amounts of Cytosine and Guanine. Chargaff proposed that these bases pair with one another in some way.

Wilkins and Franklin Rosalind Franklin and Maurice Wilkins worked with X-ray crystalography to find more clues about the structure of DNA. Franklin’s X-ray images suggested a helical structure.

Franklin and Wilkins

Watson and Crick James Watson and Francis Crick were also working on discovering the structure of DNA. Applied Chargaff’s rule, assumed that A always pairs with T, C with G. Watson was not entirely convinced of the helical structure that Franklin had suggested, and his critique of her work led her to doubt herself.

Watson and Crick Wilkins consulted with Watson and Crick. Without Franklin’s knowledge, he handed them the data that he and Franklin had worked on. Watson immediately recognized the significance. He and Crick went to work on a model of DNA.

The First DNA Model

DNA structure DNA is made up of four bases. RNA also has four bases, but has uracil instead of thymine.

DNA structure Across the DNA double-ladder, A always pairs with T, C always pairs with G because of the number of hydrogen bonds the bases form.

DNA structure The DNA ladder forms a spiral, or helical, structure, with the two sides held together with hydrogen bonds.

Marshall Nirenmberg Question: how did DNA directed the expression of proteins, or what role RNA had in these processes? They produced RNA composed solely of uracil, a nucleotide that only occurs in RNA. They then added this synthetic poly-uracil RNA into a cell-free extract of E. coli which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They then added 1 radioactively labeled amino acid.Only in the extract containing the radioactively labeled phenylalanine (UUU), was the resulting protein also radioactive. This was the first step in deciphering the codons of the genetic code and the first demonstration of messenger RNA

Meselson and Stahl In the semiconservative hypothesis, the two strands of a DNA molecule separate during replication. Each strand then acts as a template for synthesis of a new strand.[2] The conservative hypothesis proposed that the entire DNA molecule acted as a template for the synthesis of an entirely new one. The dispersive hypothesis breaks the DNA backbone every 10 nucleotides or so, untwists the molecule, and attaches the old strand to the end of the newly synthesized one. This would synthesize the DNA in short pieces alternating from one strand to the other

DNA Replication Before cells divide, they must double their DNA so that each cell gets identical copies of the DNA strands. DNA replication helps assure that the bases are copied correctly. Enzymes carry out the process.

Overview of DNA replication Overview of DNA replication. The hydrogen bonds break to “unzip” the DNA strand. Enzymes guide free nucleotides to the exposed single strands and match the nucleotides.

This diagram from your textbook (page 157) shows how enzymes carry out the replication process. DNA Helicase unzips the DNA. DNA Polymerase synthesizes the new strands, using the old strands as templates.

Linus Pauling Using electrophoresis, they demonstrated that individuals with sickle cell disease had a modified form of hemoglobin in their red blood cells, and that individuals with sickle cell trait had both the normal and abnormal forms of hemoglobin. This was the first demonstration causally linking an abnormal protein to a disease, and also the first demonstration that Mendelian inheritance determined the specific physical properties of proteins, not simply their presence or absence – the dawn of molecular genetics

Summary DNA is a nucleic acid made up of nucleotides. The order of the nucleotides is important, and is maintained by matching of bases across the DNA ladder (A-T, C-G), and by enzymes that patrol the DNA DNA replication occurs before cell division, and is an orderly, enzyme-driven process.