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Unformatted text preview: 15-1Cell and Molecular Biology (Biol. Chem. 410A)Lecture #15Harry R. Matthews, Ph.D.October 16, 1996DNA StructureClinical correlations:•diagnosis of genetic diseasesLearning objectives:•primary structure•secondary structure•domains, supercoiling•denaturation, renaturation, hybridizationOptional reading:•Stryer IV: Chapter 4.•Alberts et al.: 3rd Ed., Chapter 3, pages. 98-104; Chapter 6, 251-262.eoxyribonucleic acid (DNA) is the hereditary material of all cells. The last twenty years have seen enormous strides in our understanding of DNA and in our ability to manipulate it. This progress has already led to important clinical advances (e.g., Human Growth Factor, Tissue Plasmino-gen Activator, new diagnostic tools), but we are still only at the initial stages of applying this powerful new knowledge. The next twenty years will see equally large strides in the application of our knowledge of DNA to clinical problems.DStructure of DNA.The gross chemical structure of DNA provides a simple conceptual understanding of genetic processes. The detailed structure is beginning to be understood and the Human Genome Project is aimed at a complete low-level de-scription of human DNA.DNA is a polymer of just 4 different sub-units, or base pairs, bp. The human genome includes the DNA that codes for all the pro-teins in the body. The human genome consists of about 3 billion bp in 24 molecules of DNA found in the chromosomes (22 autosomes + 2 sex chromosomes). Each molecule is a linear, unbranched, polymer of great length (on the order of centi-meters) in comparison to its width of 2 nm. The four subunits are modi-fied deoxyribose sugars, with phosphate groups substituted for the 3' and 5' hydroxyls and a base attached at the 1' posi-tion. Only the bases vary between the subunits. The structures are shown in Fig-ure 15-1.Figure 15-1. Structure of Deoxyribonucleotides.15-2Note the nomenclature:the bases are adenine, cytosine, guan-ine, and thymine; the deoxyribonucleosides are specific nucleosides, comprised of a base + sugar, (deoxyadenosine, deoxycytid-ine, deoxyguanosine, and thymidine); the deoxyribonucleotides are specific nucleotides, comprised of a nucleos-ide + phosphate(s), e.g. deoxyaden-osine-5'-phosphate; andthe deoxyribonucleic acid is a specific polynucleotide, comprised of a poly-mer of nucleotides.The backbone of the polymer is formed from the sugar-phosphates and the bases form side-chains as shown in Figure 15-1....
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