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Unformatted text preview: 1 DNA STRUCTURE AND REPLICATION Introduction The molecule that carries the genetic information is DNA-deoxyribonucleic acid. This was discovered in the 1940s and early 50s in a series of experiments. The first and most easily understood was carried out by Avery and his colleagues. They worked with two strains of pneumococci bacteria, one pathogenic, capable of causing pneumonia in mice, and the other non-pathogenic. The pathogenic strain formed smooth colonies (masses of cells) on semi-solid media in petri dishes while the avirulent strain formed rough colonies. This difference arises from a polysaccharide coat that the virulent strain has which both allow it to be virulent and gives colonies the smooth appearance. If cells from the smooth colonies were injected in mice, the mice died of pneumonia, but if the cells were heat-killed, the mice survived. Cells from the rough colonies did not cause pneumonia, but if injected into mice along with heat-killed smooth cells, the mice did die, and only live smooth, virulent type cells could be recovered from the dead mice. Avery and his colleagues demonstrated that DNA and only DNA prepared from the smooth cells was the active agent in transferring the genes for the polysaccharide coat, and, therefore, virulence and smooth colony appearance to avirulent, rough cells. The rough cells took up DNA from the medium and became transformed to virulence. We will discuss this process of transformation in detail later. Once experiments like these established DNA as the molecule of inheritance, there was an intensive, and competitive, search to learn the structure of DNA, ultimately solved in 1953 by James Watson and Francis Crick. Before we discuss the structure of DNA, we should consider that a molecule which carries the genetic information must have three important properties: 1. It must be capable of faithful replication so that when a cell divides, it can be passed on to the two progeny cells. 2. It must be capable of carrying information. 3. It must be capable of variation within a limited context to allow diversity within a species and the evolution of new species. It is the beauty of the structure of DNA that it is immediately obvious how these three requirements for the properties of the genetic material are satisfied. 2 DNA Structure Monomers- Nucleotide structure plus base and sugar numbering Nitrogen Bases Pyrimidines 1. Cytosine 2. Thymine Purines 1. Guanine 2. Adenine Deoxyribose-sugar Phosphate Monomer structure 5'C of deoxyribose to phosphate 1'C of deoxyribose to 1N of Pyrimidine 1'C of deoxyribose to 9N of Purine Polymer Single-strand structure Covalent 5',3' phosphodiester bonds Single-strand has defined 5'to 3' polarity Double-stranded structure-weak interactions Base pairing A-T, two H-bonds G-C, three H-bonds Base stacking-interactions between nitrogen base rings The stability of the double-helix derived from the sum of the base pairing and stacking interactions over many, many base pairs The strands are oriented in the opposite polarity with respect to each other...
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