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Understand DNA's history, structure, replication, and genetic roles. Explore Griffith's experiments, Hershey-Chase experiment, DNA bases, double helix, gene definition, chromatin, and DNA replication mechanisms. Discover enzymes involved in replication.
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Human Genetics Concepts and Applications Eighth Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley
Roles of the Genetic Material “A genetic material must carry out two jobs: duplicate itself and control the development of the rest of the cell in a specific way.” -Francis Crick
History of DNA Friedrich Miescher, 1871 • Isolated white blood cell nuclei from pus • Found an acid substance with nitrogen and phosphorus • He called it “nuclein,” later called nucleic acid
History of DNA Archibald Garrod, 1902 • Linked inheritance of “inborn errors of metabolism” with the lack of particular enzyme proteins • Alkaptonuria
Bacterial Transformation Frederick Griffith, 1928 • Diplococcus pneumoniae infects mice • Mice develop pneumonia and die Two types of bacteria: • R bacteria rough coat no pneumonia • S bacteria smooth coat pneumonia • Coat type is associated with virulence.
Griffith’s Experiments Figure 9.1
The “Transforming Principle” • Avery, MacLeod, and McCarty, 1944 • Treated lysed S bacteria with protease and DNase • DNase prevented transformation • Therefore DNA is the transforming principle Figure 9.2
DNA Is the Genetic Material Alfred Hershey and Martha Chase, 1953 • Viruses can infect the E. coli bacteria • A virus has protein “head” and DNA core • Used radioactive S and P to label protein and DNA • Virus injects DNA into a bacterial cell
Hershey-Chase Experiment DNA Is the Genetic Material Figure 9.3
The Structure of DNA Levine, 1909 • Identified the sugar, ribose • 1929, identified deoxyribose • Three parts of a nucleotide • Sugar • Phosphate • Base
Deoxyribonucleic Acid (DNA ) • Subunits are deoxyribonucleotides • Composed of: • Sugar deoxyribose • Phosphate group • Base one of four types: • adenine (A), thymine (T) • guanine (G), cytosine (C)
DNA Deoxyribose Phosphate Figure 9.7 Figure 9.6 Bases: G A, C, and T
DNA Bases Pair Erwin Chargaff observed: Within an individual • Adenine = Thymine • Guanine = Cytosine Because • Complementary bases pair by hydrogen bonds: A with T C with G
DNA Forms a Double Helix • Maurice Wilkins and Rosalind Franklin • The clue from photo 51 • X-ray diffraction indicated DNA is a helix Figure 9.4
Watson and Crick’s Model of DNA • A sugar and phosphate “backbone” • Two nucleotide chains in a helix. • Hydrogen bonds hold the two strands together • DNA strands are antiparallel Figure 9.5
Orientation of DNA The 5’ phosphate of one nucleotide is attached to the 3’ hydroxyl group of the previous nucleotide The directionality of a DNA strand is due to the orientation of the phosphate-sugar backbone Figure 9.11
Molecular Definition of a Gene • A gene is a segment of DNA • It directs the formation of RNA to produce protein • The protein (or functional RNA) creates the phenotype • Information is conveyed by the sequence of the nucleotides
Chromatin • Composed of DNA and associated proteins • DNA winds around histone proteins • (nucleosomes) • Other proteins wind DNA more tightly to form a chromosome • During mitosis, replication and mRNA production DNA is unwound
Replication Production of new copies of the DNA molecules,occurs in S of interphase prior to cell division Potential mechanisms: organization of DNA strands Conservative old/old + new/new Semiconservative old/new + new/old Dispersive mixed old & new
Replication • Meselson and Stahl, 1957 • Labeled newly synthesized DNA with heavy nitrogen (15N) • Density shift experiments with bacteria • Traced replicating DNA • Determined DNA replicates semiconservatively
Replication as a Process • Double-stranded DNA unwinds. • The junction of the unwound molecules is a replication fork. • A new strand is formed by pairing complementary bases with the old strand. • Two molecules are made. • Each has one new and one old DNA strand • Two sister chromatids are formed .
Overview Figure 9.15
Enzymes in DNA Replication Figure 9.16
Replication Figure 9.17 Helicase protein binds to DNA sequences called origins and unwinds DNA strands.
Replication Figure 9.16 DNA polymerase adds DNA nucleotides to the RNA primer and replaces incorrect nucleotides
Replication Figure 9.16 • Leading strand synthesis continues in a 5’ to 3’ direction • Discontinuous synthesis produces 5’ to 3’ DNA • segments called Okazaki fragments
Replication Figure 9.16 Exonuclease enzymes remove RNA primers Ligase forms bonds between sugar-phosphate backbone