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The Brief History of DNA • Discovery of the DNA double helix Frederick Griffith – Discovers that a factor in diseased bacteria can transform harmless bacteria into deadly bacteria (1928) He called this the transforming principle, and thought it was a protein responsible for this transference. Rosalind Franklin – Used X-ray crystallography photo of DNA. The discovery of its structure helped scientists understand how genetic information was passed from parents to children (1952) Watson and Crick - described the DNA molecule from Franklin’s X-ray. (1953) • Griffith: bacterial work; transformation: change in genotype and phenotype due to assimilation of external substance, which he thought was protein, by a cell (1928) • Avery: hereditary agent was DNA, not protein group proved this by adding protein digesting enzymes (1944) Avery’s to the mix, and then DNA digesting enzymes, and observing the reactions. Exposure to DNA digesting enzymes blocked the transformation. During the cellular reproductive processes, such as mitosis and meiosis, DNA must replicate itself. Replication happens during the “S” or synthesis phase of interphase of the cell cycle. Exactly how does replication happen? First, a portion of the DNA double helix unwinds through the work of an enzyme called helicase, which serves to break the hydrogen bonds between the nitrogenous bases. The section that opens up in the DNA molecule is called a replication fork. As this replication fork opens up, it exposes the 3’ and the 5’ ends of the original DNA strand. In this diagram, that is represented by the blue molecule. • An enzyme known as DNA polymerase adds nucleotides to the original strand’s free 3’ end, in a continuous fashion. The new DNA strand is therefore forming from a 5’ direction, and is referred to as the “leading strand”. • On the open 5’ end, the new Assembly is discontinuous because DNA is built in a discontinuous the exposed –OH group on the 3’ fashion, from the region nearest end is the only place where the fork opening. This new strand nucleotides can be joined together. is known as the “lagging strand”. DNA ligase then helps to join the Okazaki fragments are formed, or fragments and wind the strands back up little “chunks” of DNA. into a double helix. When DNA replication occurs, it begins somewhere in the middle of the molecule, and not at one end. The “replication fork” is within the bubble. As the new molecules are built, they progress in opposite directions from the point of origin. DNA Replication • Semiconservative Model: This model is referred to as semiconservative, because half of every newly constructed DNA molecule is old, and from the “parent” DNA. 1. Watson and Crick showed: the two strands of the parental molecule separate, and each functions as a template for synthesis of a new complementary strand. Parental DNA DNA Template New DNA When the process is complete, two DNA molecules have been formed identical to each other and to the parent molecule Errors during replication are rare, as each cell contains a family of more than thirty enzymes to ensure the accurate replication of DNA DNA polymerase makes very few errors, and most of those that are made are quickly corrected by DNA polymerase which "proofreads" the nucleotides added into the new DNA strand. If a non-complementary nucleotide is added in error, enzymes remove the nucleotide and replace it with the correct one. A cell’s DNA is copied with less than one mistake in a billion nucleotides! This is equal to a person copying 100 large (1000 page) dictionaries word for word, and symbol for symbol, with only one error for the whole process!