DNA the carrier of genetic information

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DNA the carrier of genetic information

  1. 1. How does the DNA lead to specific traits??? Archibald Garrod (1909) hypothesized: “proteins are the link between genotype & phenotype”
  2. 2. 1909 - Archibald Garrod  Suggested genes control enzymes, & enzymes catalyze chemical processes in cells. Inherited Diseases are “inborn errors of metabolism” where a person can’t make an enzyme.”
  3. 3. Example Alkaptonuria  where urine turns black after exposure to air
  4. 4. enzyme enzyme enzyme enzyme
  5. 5. • G. Beadle & Edward Tatum Nobel Prize in Physiology or Medicine 1958 "for their discovery that genes act by regulating definite chemical events"
  6. 6. One Gene, One Enzyme Hypothesis -Beadle & Tatum  each gene dictates the production of one enzyme  each mutant lacks the ability to produce an enzyme
  7. 7. *Some proteins are not enzymes (ex. insulin) *Some proteins are made of more than one polypeptide chain (hemoglobin) *Each chain specified by its own gene One Gene, One Polypeptide Hypothesis -Beadle & Tatum (revisited)
  8. 8.  Evidence of DNA as hereditary material › Proteins rather than nucleic acids thought to be genetic material in the 1930s and 1940s › Several lines of evidence supported DNA as genetic material  DNA is transforming principle in bacteria › Watson and Crick modeled DNA structure
  9. 9. Griffith’s transformation experiments Oswald Avery Frederick Griffith Colin MacLeod
  10. 10. Established that DNA carries necessary information for bacterial transformation
  11. 11.  Avery–MacLeod–McCarty experiment
  12. 12. Hershey-Chase experiments Established that viral DNA enters bacterial cells and is required for synthesis of new viral particles Alfred Hershey Martha Chase
  13. 13.  Structure of DNA › Regular polymer of nucleotides  Nitrogenous base of purine or pyrimidine  Base covalently links to deoxyribose  Deoxyribose covalently bonds to a phosphate group › Backbone  Alternating sugar and phosphate groups joined by covalent phosphodiester linkages
  14. 14. Nucleotide subunits of DNA
  15. 15. x-ray diffraction studies Carried out by Rosalind Franklin on crystals of purified DNA Born: July 25, 1920 Died: April 16, 1958
  16. 16. X-ray diffraction image of DNA
  17. 17.  three major types of regular, repeating patterns in the molecule with the dimensions 0.34 nanometer, 3.4 nanometers, and 2.0 nanometers were evident.
  18. 18.  Watson and Crick began to pursue the problem of DNA structure  each pair of bases is exactly 0.34 nanometer from the adjacent pairs above and below  Because exactly ten base pairs are present in each full turn of the helix, each turn is 3.4 nanometers high  DNA molecule is 2.0 nm wide.
  19. 19.  Structure of DNA molecule › Two polynucleotide chains associated as double helix › Two chains are antiparallel (running in opposite directions) › The sugar-phosphate backbones of the two chains form the outside of the helix › The bases belonging to the two chains associate as pairs in the center
  20. 20. 3-D model of DNA double helix James D. Watson Francis Crick
  21. 21. Erwin Chargaff the base composition of DNA from a number of organisms and tissues had been determined Regardless of the source of the DNA “ratios of purines to pyrimidines and also of adenine to thymine and ofguanine to cytosine were not far from 1.
  22. 22. Base compositions in DNA from selected organisms
  23. 23.  Base-pairing rules for DNA › Hydrogen bonding between base pairs holds together the two chains of helix › Adenine (A) forms two hydrogen bonds with thymine (T) › Guanine (G) forms three hydrogen bonds with cytosine (C) › Chargaff’s rules A=T G=C
  24. 24. Base pairing and hydrogen bonding
  25. 25.  DNA replication modes
  26. 26.  DNA REPLICATION is SEMICONSERVATIVE  One way to accomplish this is to use a heavy-nitrogen isotope,nitrogen-15 (ordinary nitrogen is nitrogen-14)  Matthew Meselson and Franklin Stahl grew cells of the bacterium Escherichia coli on a medium that contained nitrogen-15 in the form of ammonium chloride (NH4Cl) Matthew Meselson Franklin Stahl
  27. 27.  DNA Replication › Two strands of double helix unwind › Each strand serves as template for new strand › DNA polymerase adds new nucleotide subunits › Additional enzymes and other proteins required to unwind and stabilize DNA helix
  28. 28. › Bidirectional, starting at origin of replication › Strands replicate at replication fork › Two DNA polymerase molecules catalyze replication  Leading strand  Lagging strand
  29. 29. Enzymes involved in DNA replication
  30. 30. Simplified view of DNA replication
  31. 31. Overview of DNA replication
  32. 32. Leading and lagging DNA strands
  33. 33. Bidirectional DNA replication in bacteria and eukaryotes
  34. 34.  Replication › Telomeres at chromosome ends  Short, non-coding repetitive DNA sequences  Shorten slightly with each cell cycles  Can be extended by telomerase  Absence of telomerase activity may be cause of cell aging › Most cancer cells have telomerase to maintain telomere length and resist apoptosis
  35. 35. Replication at chromosome ends

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