Chapter 16 The Molecular Basis of Inheritance

1. Chapter 16The Molecular Basis of Inheritance

2. You Will Be Able To: • Describe historical experiments that lead to the model for the DNA structure • Describe the overall structure of DNA • Explain how DNA matches up base pairs • Diagram DNA replication • Explain the role of telomeres and telomerase in cell functions

3. Evidence of DNA as hereditary material: -Proteins—rather than nucleic acids— thought to be genetic material in 1930s and 1940s. • Several lines of evidence supported DNA as genetic material.

4. DNA carries necessary info for bacterial Transformation 1928: Frederick Griffith’s transformation experiments

5. Finds substance in heat-killed bacteria that transforms living bacteria. 1928: Frederick Griffith’s transformation experiments

6. 1944: Avery, MacLeod, McCarty Chemically identify Griffith’s transforming factor as

7. 1949: Erwin Chargaff • Reports relationship among DNA bases that gives a clue about DNA structure

8. 1952: Hershey and Chase Demonstrate that DNA, not a protein, is involved in viral reproduction

9. 1952: Hershey and Chase Demonstrate that DNA, not a protein, is involved in viral reproduction

10. Hershey-Chaseexperiments: Established that viral DNA enters bacterial cells DNA is required for

11. 1952: Rosalind Franklin Produces X-ray diffraction of DNA molecule

12. 1953: Watson and Crick • Propose a model of DNA structure based on Franklin’s X-ray image and lectures

13. 1958: Meselson and Stahl Show that DNA replication is semi-conservative

14. Structure of DNA: • Regular polymer of nucleotides: • -Nitrogenous bases made up of either • a purine • a pyrimidine • -Base covalently links to deoxyribosesugar ring • -Deoxyribose also covalently bonds to a • phosphate group

15. Structure of DNA: • DNA Backbone; • Alternating sugar &phosphategroups

16. Carbon numbers on DNA describe where phosphodiester bonds form

17. Name the parts of a nucleotide Nucleotide subunits of DNA Which parts are associated with the side chains? Which parts compose the “rungs” connecting the sides?

18. Structure of DNA molecule: • Two polynucleotide chains associated together as a • The 2chains are antiparallel

19. Structure of DNA molecule: “Rungs” are pairs of nitrogenous bases • But what combination of bases? • How did they find out? • Erwin Chargaff analyzed DNA - looked for

20. Base compositions in DNA from selected organisms Erwin Chargaff showed that all DNA molecules, from all kinds of organisms,

21. 3-D model of DNA double helix DNA structure was exceedingly important to the entire field of genetics Structure and function are intertwined in biological systems

22. _____________________holds key for understanding how DNA works

23. Base-pairing rules for DNA • H bonding btwnbase pairs holds 2chains of helix together (“rungs”) • Adenine (A) forms 2 H bonds with thymine (T) • Guanine (G) forms 3 H bonds with cytosine (C) • Chargaff’s rules:

24. Base pairingand H bonding: Intermolecular H bonds

25. 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

26. DNA helicases Special enzyme: travels down “rungs” of DNA H bonds are ____________ btwn nitrogenous base pairs DNA double helix “unzipped” Single strand binding proteins

27. DNA helicases

28. Topoisomerases • Special enzyme that breaks DNA at other sites, then rejoins the pieces

29. Topoisomerase at work

30. DNA primase Makes a short (5 to 14 nucleotides long) RNA strand to get the replication started DNA polymerase takes over and continues to _______________________ Later, enzymes break up the RNA piece ____________________________

31. DNA primase enzyme “primes” the replicating machine with an

32. DNA polymerase This enzyme helps link nucleotides together: makes a polymer of DNA Only link nucleotides to the 3’ carbon end of a DNA chain (-OH group) (not the phosphate end – 5’ carbon)

33. DNA polymerase Links to 3’ C end

34. DNA ligase Lagging strand is made up of sections: Called: 100 to 2,000 nucleotide pieces DNA ligase hooks 3’ hydroxyl end of an Okazaki fragment to a 5’ (phosphate) end of the new DNA strand

35. DNA ligase fusing Okazaki pieces together

36. Bi-directional, starting at origin of replication DNA replication • Strands replicate at replication fork • Two DNA polymerase molecules • catalyze replication

37. Leading strand: continuously made – Lagging strand: short pieces connected - DNA replication

38. Telomeres Ends of linear DNA strands break down with each cell division Protein info is NOT lost! Ends of DNA are special pieces of

39. Telomerase is a special enzyme:

40. Replication at chromosome ends • Telomeres(like shoelace tips) • 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 & death

41. Replicationatchromosomeends RNA primer removed at end of replication

42. Simplified view of DNA replication Free nucleotides match to a base Connects to growing strand

43. Overview of DNA replication

44. LeadingandlaggingDNAstrands

45. DNA replication Can you name each step and associated enzymes?

46. Prokaryotic DNA • The main DNA in prokaryotes is • Some DNA is organized in smaller circles

47. Prokaryotic DNA • 90% of the genome consists of • Genes coding for a metabolic pathway are lumped together into an ____________

49. Eukaryotic cells’ DNA differs considerably from prokaryotic cells’ DNA Consider this: • most DNA (~90 %) on eukaryotic chromosomes is non-coding • Nobody knows why…

50. Review and Test Yourself to See if You Met The Learning Objectives: • Describe historical experiments that lead to the model for the DNA structure • Describe the overall structure of DNA • Explain how DNA matches up base pairs • Diagram DNA replication • Explain the role of telomeres and telomerase in cell functions