1. BIOLOGY CONCEPTS & CONNECTIONS Fourth Edition Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Neil A. Campbell Jane B. Reece Lawrence G. Mitchell Martha R. Taylor From PowerPoint ® Lectures for Biology: Concepts & Connections CHAPTER 10 Molecular Biology of the Gene Modules 10.1 – 10.5

2. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The invasion and damage of cells by the herpesvirus can be compared to the actions of a saboteur intent on taking over a factory –The herpesvirus hijacks the host cell’s molecules and organelles to produce new copies of the virus Saboteurs Inside Our Cells

3. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Viruses provided some of the earliest evidence that genes are made of DNA Molecular biology studies how DNA serves as the molecular basis of heredity

4. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings In 1928, Frederick Griffith, an English army doctor, wanted to make a vaccine against a bacteria named Streptococcus pneumoniae, which caused a type of pneumonia. Since the time of Pasteur, about 50 years before, vaccines had been made using killed microorganisms which could be injected into patients to elicit the immune response of live cells without risk of disease. Though he failed in making the vaccine he stumbled on a demonstration of the transmission of genetic instructions by a process we now call the "transformation principle".Frederick GriffithPasteur

5. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Experiments showed that DNA is the genetic material

6. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings What was the transforming principal??????

7. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Experiments showed that DNA is the genetic material

8. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings

9. DNA was the genetic, transforming principal…. Oswald Avery: the professor, DNA, and the Nobel Prize that eluded him. Professor Emeritus of Pathology, Dalhousie University. In 1944, two Canadians, Oswald Avery and Colin MacLeod, and an American, McCarty, published a paper in The Journal of Experimental Medicine that demonstrated genes to be the chemical, deoxyribonucleic acid (DNA). Even though this paper is now regarded as the single most important publication in biology of the 20th century, Avery was not awarded the Nobel Prize. This raises the question as to why his work did not earn him the Prize. These are several possible reasons: the discovery may have been ahead of tis time; all three authors were physician-scientists and not recognized chemists or geneticists; and Avery, the principal author, had reached an advanced age and characteristically took an extremely cautious and low-key approach to his work. Discussion of these reasons in turn raises other issues surrounding the recognition of the work of celebrated scientist, from Galileo and Copernicus onwards.

10. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The Hershey-Chase experiment showed that certain viruses reprogram host cells to produce more viruses by injecting their DNA Experiments showed that DNA is the genetic material Head Tail Tail fiber DNA Figure 10.1A

11. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Phage reproductive cycle Figure 10.1C Phage attaches to bacterial cell. Phage injects DNA. Phage DNA directs host cell to make more phage DNA and protein parts. New phages assemble. Cell lyses and releases new phages.

12. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The Hershey-Chase Experiment Figure 10.1B Mix radioactively labeled phages with bacteria. The phages infect the bacterial cells. Phage Bacterium Radioactive protein DNA Empty protein shell 12 Agitate in a blender to separate phages outside the bacteria from the cells and their contents. 3 Centrifuge the mixture so bacteria form a pellet at the bottom of the test tube. 4 Measure the radioactivity in the pellet and liquid. Batch 1 Radioactive protein Batch 2 Radioactive DNA Radioactive DNA Phage DNA Centrifuge Pellet Radioactivity in liquid Radioactivity in pellet Pellet Centrifuge

13. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings For his fundamental contributions to molecular biology, Hershey received the 1958 Albert Lasker Award and the 1965 Kimber Genetics Award. However, it was not until 1969 that Hershey, together with Delbrück and Luria, was awarded the Nobel Prize for physiology or medicine. Martha Chase was a lab assistant in the 1950’s and did not receive the Nobel Prize for her work.

14. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings DNA is a nucleic acid, made of long chains of nucleotides DNA and RNA are polymers of nucleotides Figure 10.2A Nucleotide Phosphate group Nitrogenous base Sugar PolynucleotideSugar-phosphate backbone DNA nucleotide Phosphate group Nitrogenous base (A, G, C, or T) Thymine (T) Sugar (deoxyribose)

15. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings DNA has four kinds of bases, A, T, C, and G Figure 10.2B Pyrimidines Thymine (T)Cytosine (C) Purines Adenine (A)Guanine (G)

16. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Note the designation of the Carbons as 1-5.

17. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings James Watson and Francis Crick worked out the three-dimensional structure of DNA, based on work by Rosalind Franklin 10.3 DNA is a double-stranded helix Figure 10.3A, B

18. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The structure of DNA consists of two polynucleotide strands wrapped around each other in a double helix Figure 10.3C Twist 1 chocolate coat, Blind (PRA)

19. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Hydrogen bonds between bases hold the strands together –Each base pairs with a complementary partner –A pairs with T –G pairs with C Chargaff’s Rule

20. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Three representations of DNA Figure 10.3D Ribbon modelPartial chemical structureComputer model Hydrogen bond

21. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings right-handed A-formB-form Z-form right-handed left-handed

22. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings In DNA replication, the strands separate –Enzymes use each strand as a template to assemble the new strands DNA REPLICATION 10.4 DNA replication depends on specific base pairing Parental molecule of DNA Figure 10.4A Both parental strands serve as templates Two identical daughter molecules of DNA Nucleotides A A

23. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Untwisting and replication of DNA Figure 10.4B

24. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings DNA replication begins at specific sites 10.5 DNA replication: A closer look Figure 10.5A Parental strand Origin of replication Bubble Two daughter DNA molecules Daughter strand

25. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Tid Bits 1. If multiple sites were not being replicated simultaneously: –Fruit fly DNA would take 16 days to replicate only 8 chromosomes –In bacteria, 500 nucleotides are being added per second/ eukaryotes are adding 50 nucleotides per second. 2. Replication must take place in a 5’ to 3’ direction and the DNA strand is antiparallel 3. Eukaryotes have directional issues and telomere issues!!! (To be discussed soon, stay tuned)

26. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Each strand of the double helix is oriented in the opposite direction Nucleotides can only be added to the free 3’ end of the DNA strand. There is only 1 error per billion base pairs!! Figure 10.5B 5 end3 end 5 end P P P P P P P P

27. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings How DNA daughter strands are synthesized –5’ – 3’ direction 5 end P P Parental DNA Figure 10.5C DNA polymerase molecule 5 3 3 5 3 5 Daughter strand synthesized continuously Daughter strand synthesized in pieces DNA ligase Overall direction of replication 5 3 The daughter strands are identical to the parent molecule

28. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The Enzymes of DNA Synthesis

29. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings DNA polymerase I fills in the spaces between the Okasaki Fragments. DNA polymerase III adds nucleotides to the “free 3.” Gyrase unwinds the DNA by catalyzing the formation of negative supercoils. Helicase separates the strands. DNA polymerase II is a prokaryotic DNA polymerase most likely involved in DNA repair prokaryoticDNA polymeraseDNA repair

30. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings

31. The initial requirement for a free 3' hydroxyl group is fulfilled by the RNA primers that are synthesized at the initiation sites by primase enzymes.

32. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings RNA is also a nucleic acid –RNA has a slightly different sugar –RNA has U instead of T Figure 10.2C, D Phosphate group Nitrogenous base (A, G, C, or U) Uracil (U) Sugar (ribose)