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3. 2 DNA DNA.DNA is often called the blueprint of life. In simple terms, DNA contains the instructions for making proteins within the cell.

4. 3 History of DNA

5. 4 Early scientists thought protein was the cell’s hereditary material because it was more complex than DNA Proteins were composed of 20 different amino acids in long polypeptide chains

6. 5 History of DNA Chromosomes are made of both DNA and protein Experiments on bacteriophage viruses by Hershey & Chase proved that DNA was the cell’s genetic material Radioactive 32 P was injected into bacteria!

7. 6 Discovery of DNA Structure Erwin Chargraff showed the amounts of the four bases on DNA ( A,T,C,G) In a body or somatic cell: A = 30.9% T = 29.4% G = 19.9% C = 19.8%

8. 7 Chargaff’s Rule Adenine Thymine A - TAdenine must pair with Thymine A - T Guanine Cytosine G - CGuanine must pair with Cytosine G - C The bases form weak hydrogen bonds G C TA

9. 8 DNA Structure Rosalind Franklin took diffraction x- ray photographs of DNA crystals In the 1950’s, Watson & Crick built the first model of DNA using Franklin’s x-rays

10. 9 Watson & Crick’s Model 1953 Watson & Crick proposed that DNA is composed of two strands of nucleotides held together by nitrogenous bases in the form of a double helix.

11. 10 DNA Why do we study DNA? We study DNA for many reasons, e.g., its central importance to all life on Earth, medical benefits such as cures for diseases, better food crops.

12. 11 Chromosomes and DNA Our genes are on our chromosomes. Chromosomes are made up of a chemical called DNA.

13. 12 The Shape of the Molecule DNA is a very long polymer. The basic shape is like a twisted ladder or zipper. This is called a double helix.

14. 13 The Double Helix Molecule The DNA double helix has two strands twisted together. These strands run antiparallel. 3’-5’ & 5’-3’

15. 14 One Strand of DNA The backbone of the molecule is alternating phosphates and deoxyribose sugar The teeth are nitrogenous bases. phosphate deoxyribose bases

16. 15 Nucleotides CC C O Phosphate O C C O -P O O O O O O O One deoxyribose together with its phosphate and base make a nucleotide. Nitrogenous base Deoxyribose

17. 16 One Strand of DNA One strand of DNA is a polymer of nucleotides. One strand of DNA has many millions of nucleotides. nucleotide

18. 17 Four nitrogenous bases Cytosine C Thymine T Adenine A Guanine G DNA has four different bases:

19. 18 Two Kinds of Bases in DNA Pyrimidines are single ring bases.Pyrimidines are single ring bases. Purines are double ring bases.Purines are double ring bases. C C C C N N O N C C C C N N N N N C

20. 19 Thymine and Cytosine are pyrimidines Thymine and cytosine each have one ring of carbon and nitrogen atoms.Thymine and cytosine each have one ring of carbon and nitrogen atoms. C C C C N N O N cytosine C C C C N N O O thymine C

21. 20 Adenine and Guanine are purines Adenine and guanine each have two rings of carbon and nitrogen atoms.Adenine and guanine each have two rings of carbon and nitrogen atoms. C C C C N N N Adenine N N C C C C C N N O N Guanine N N C

22. 21 Two Stranded DNA Remember, DNA has two strands that fit together something like a zipper. The teeth are the nitrogenous bases but why do they stick together?

23. 22 C C C C N N O N C C C C N N O N N N C Hydrogen Bonds The bases attract each other because of hydrogen bonds. Hydrogen bonds are weak but there are millions and millions of them in a single molecule of DNA. The bonds between cytosine and guanine are shown here with dotted lines

24. 23 Hydrogen Bonds, Hydrogen Bonds, cont. When making hydrogen bonds, cytosine always pairs up with guanine Adenine always pairs up with thymine Adenine is bonded to thymine here C C C C N N N N N C C C C C N N O O C

25. 24 DNA by the Numbers Each cell has about 2 m of DNA. The average human has 75 trillion cells. The average human has enough DNA to go from the earth to the sun more than 400 times. DNA has a diameter of only 0.000000002 m. The earth is 150 billion m or 93 million miles from the sun.

26. 25 DNA and Replication

27. 26 Antiparallel Strands One strand of DNA goes from 5’ to 3’ (sugars) The other strand is opposite in direction going 3’ to 5’ (sugars)

28. 27 Replication Facts DNA has to be copied before a cell dividesDNA has to be copied before a cell divides DNA is copied during interphase of mitosisDNA is copied during interphase of mitosis New cells will need identical DNA strandsNew cells will need identical DNA strands Occurs in many spot on a chromosomeOccurs in many spot on a chromosome

29. Three Phases of Replication Initiation: Unzipping DNA Elongation: Making new DNA strand Termination: Ends at telomeres (specific repeated bases) Zipping DNA back together.

30. 29 DNA Replication Begins at Origins of ReplicationBegins at Origins of Replication Two strands open forming Replication Forks (Y- shaped region) The “unzipping of the DNA strand is carried out by an enzyme DNA helicase.Two strands open forming Replication Forks (Y- shaped region) The “unzipping of the DNA strand is carried out by an enzyme DNA helicase. New strands grow at the forksNew strands grow at the forks ReplicationFork Parental DNA Molecule 3’ 5’ 3’ 5’

31. 30 DNA Replication Enzyme Helicase unwinds and separates the 2 DNA strands by breaking the weak hydrogen bondsEnzyme Helicase unwinds and separates the 2 DNA strands by breaking the weak hydrogen bonds Single-Strand Binding ProteinsSingle-Strand Binding Proteins attach and keep the 2 DNA strands separated and untwisted

32. 31 DNA Replication Before RNA primersBefore new DNA strands can form, there must be RNA primers present to start the addition of new nucleotides. DNA polymerase can then add the new nucleotides

33. 32 DNA Replication DNA polymerase can only add nucleotides to the 3’ end of the DNADNA polymerase can only add nucleotides to the 3’ end of the DNA This causes the NEW strand to be built in a 5’ to 3’ directionThis causes the NEW strand to be built in a 5’ to 3’ direction RNAPrimer DNA Polymerase Nucleotide 5’ 3’ Direction of Replication

34. Leading and Lagging Strands Leading strand: starts at the 3’ end of the parent DNA forming the complementary strand of 5’ to 3’ Lagging strand: is discontinuous (patchwork for DNA); requires many RNA primers for Okazaki fragments

35. Okazki Fragment The joining of RNA primers and DNA polymerase creates an Okazaki fragment. Only occurs on lagging strand

36. Finishing the New DNA Strands DNA Ligase “zips up” the lagging DNA strand –This is done by joining the old and new strands of DNA with hydrogen bonds. 35

37. 36 Remember the Strands are Antiparallel P P P O O O 1 2 3 4 5 5 3 3 5 P P P O O O 1 2 3 4 5 5 3 5 3 G C TA

38. 37 Replication of Strands Replication Fork Point of Origin

39. 38 Proofreading New DNA DNA polymerase initially makes about 1 in 10,000 base pairing errorsDNA polymerase initially makes about 1 in 10,000 base pairing errors Enzymes proofread and correct these mistakesEnzymes proofread and correct these mistakes The new error rate for DNA that has been proofread is 1 in 1 billion base pairing errorsThe new error rate for DNA that has been proofread is 1 in 1 billion base pairing errors

40. 39 Semiconservative Model of Replication Idea presented by Watson & CrickIdea presented by Watson & Crick TheThe two strands of the parental molecule separate, and each acts as a template for a new complementary strand New DNA consists of 1 PARENTAL (original) and 1 NEW strand of DNA Parental DNA DNA Template New DNA

41. 40 DNA Damage & Repair Chemicals & ultraviolet radiation damage the DNA in our body cells –Specific or non specific repair Cells must continuously repair DAMAGED DNA Excision repair occurs when any of over 50 repair enzymes remove damaged parts of DNA DNA polymerase and DNA ligase replace and bond the new nucleotides together