1. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-1 Human Genetics Concepts and Applications Eighth Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-2 Chapter 9 DNA Structure and Replication

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-3 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

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-4 DNA Is the Genetic Material

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-5 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

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-6 History of DNA Archibald Garrod, 1902 Linked inheritance of “inborn errors of metabolism” with the lack of particular enzyme proteins Alkaptonuria

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-7 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.

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-8 Griffith’s Experiments Figure 9.1

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-9 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

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-10 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

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-11 Hershey-Chase Experiment DNA Is the Genetic Material Figure 9.3

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-12 The Structure of DNA Levine, 1909 Identified the sugar, ribose 1929, identified deoxyribose Three parts of a nucleotide – Sugar – Phosphate – Base

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-13 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)

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-14 DNA DeoxyribosePhosphate Bases: G A, C, and T Figure 9.6 Figure 9.7

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-15 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

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-16 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

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-17 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

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-18 Figure 9.9a

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-19 Figure 9.9b

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-20 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

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-21 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

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-22 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

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-23 Figure 9.13

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-24 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

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-25 Replication Meselson and Stahl, 1957 Labeled newly synthesized DNA with heavy nitrogen ( 15 N) Density shift experiments with bacteria Traced replicating DNA Determined DNA replicates semiconservatively

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-26 Figure 9.14

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-27 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.

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-28 Overview Figure 9.15

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-29 Enzymes in DNA Replication Figure 9.16

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-30 Replication Helicase protein binds to DNA sequences called origins and unwinds DNA strands. Figure 9.17

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-31 Replication DNA polymerase adds DNA nucleotides to the RNA primer and replaces incorrect nucleotides Figure 9.16

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-32 Replication Leading strand synthesis continues in a 5’ to 3’ direction Discontinuous synthesis produces 5’ to 3’ DNA segments called Okazaki fragments Figure 9.16

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9-33 Replication Exonuclease enzymes remove RNA primers Ligase forms bonds between sugar-phosphate backbone Figure 9.16