DNA The Molecule of Life


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DNA The Molecule of Life

  1. 1. The Molecule of Life: DNASalwa Hassan Teama M.D. Salwa Hassan Teama 2012Molecular Biology Department/ Medical Research CenterAin Shams University/ Cairo/ Egypt
  2. 2. Salwa Hassan TeamaDNA
  3. 3. Salwa Hassan TeamaTHE MOLECULE OF LIFE
  4. 4. The DNA The genetic material of all cellular organisms and most viruses. The gigantic molecule which is used to encode genetic information for all life on Earth. Salwa Hassan Teama
  5. 5. The Molecule of Life SALW A HASSAN TEAMA
  6. 6. The DNAWithin cells, DNA is organizedinto structures calledchromosomes.Eukaryotic organisms (animals,plants, fungi, and protists) storetheir DNA inside the cellnucleus, while in prokaryotes(bacteria and archae) it is foundin the cells cytoplasm. Salwa Hassan Teama
  7. 7. Salwa Hassan TeamaIn normal human cellDNA contained in thenucleus, arranged in 23pairs of chromosomes.
  8. 8. Human ChromosomesTwenty three pairs:Twenty two pairs ofchromosomes (autosomes);one pair determines the sexof individual and iscomposed of either (XX)(female) or (XY) (male). Salwa Hassan Teama
  9. 9. Chromosome/ Amount of DNA Table adapted from; http://www.ncbi.nlm.nih.gov/books/NBK7587/table/A657/?report=objectonly Salwa Hassan Teama
  10. 10. Sizes of Various DNAsTable adapted from: Molecular Biology. Fourth Edition. Robert F. Weaver. McGraw-Hill International Edition Salwa Hassan Teama
  11. 11. General Structure of Nucleic AcidDNA is a long chainpolymers of small compoundcalled nucleotides. Salwa Hassan Teama
  12. 12. The NucleotideEach nucleotide is composedof a base; sugar (deoxyribose)and a phosphate group. Thephosphate joins the sugars ina DNA chain through their 5and 3 hydroxyl group byphosphodiester bonds. Salwa Hassan Teama
  13. 13. Chemical Nature of PolynucleotidesThere are four different types of nucleotides found in DNA,differing only in the nitrogenous base: A is for adenine; G is forguanine; C is for cytosine and T is for thymine.The bases are classified based on their chemical structures intotwo groups: adenine and guanine are double ringed structuretermed purine , thymine and cytosine are single ring structurestermed pyrimidine. Salwa Hassan Teama
  14. 14. The Building Blocks of Nucleic Acids
  15. 15. DNA ComplementarityThe bases pair in a specificway: Adenine A withthymine T (two hydrogenbonds) and guanine G withcytosine C (threehydrogen bonds).
  16. 16. Chargaffs RulesWithin the structure ofDNA, the number ofthymine is alwaysequal to the number ofadenine, and thenumber of cytosine isalways equal toguanine. Salwa Hassan Teama
  17. 17. The Structure of DNAThe structure of DNA wasdescribed by British ScientistsWatson and Crick based onchemical and physical datathat had been gathered inother laboratories, primarily xray diffraction data collectedby Rosalind Franklin andMaurice Wilkins. Salwa Hassan Teama
  18. 18. The DNAJames D. Watson Francis Crick Rosalind Franklin Maurice Wilkins
  19. 19. April 25, 1953: JamesWatson and FrancisCricks describes thedouble helical structure ofDNA. The structuresuggests a possiblecopying mechanism forthe genetic material. Source, Cold Spring Harbor Laboratory Archives
  20. 20. April 25, 1953: RosalindFranklin and Ray Goslingprovide further evidenceof the helical nature ofnucleic acids, Rosalindfranklin used xcrystallography to helpvisualize the structure ofDNA.
  21. 21. DNA Double Helix Linked as a twisted ladder The curving sides of the ladder represent the sugar- phosphate backbone of the two DNA strands; the rungs are the base pairs Possess antiparallel polarity Stabilized by hydrogen bonds between the bases
  22. 22. DNA Double Helix Salwa Hassan Teama
  23. 23. DNA Double HelixThe strands are antiparallel. Ifone has 5 3 polarity fromtop to bottom, the other musthave 3 5 polarity from top tobottom. Salwa Hassan Teama
  24. 24. Variety of DNA Structures A Form B Form Z Form ……. Salwa Hassan Teama
  25. 25. Variety of DNA StructuresThese forms are distinguished by: The number of base pair The angle between each base pair The helical diameter of the molecule Right or left hand direction of double helix Salwa Hassan Teama
  26. 26. The B formThe most dominant form under physiological conditions,Right-handed helix,Wide major groove easily accessible to proteins; narrow minor groove,Represents the sodium salt of DNA in a fiber produced at very of relative humidity (92%),Diameter of approx. 2nm,Rise/turn of helix; 33.2 Å (3.32 nm),Inclination of bp to axis -1.2°.
  27. 27. The A FormRight-handed helix,Deep, narrow major groove not easily accessible toproteins.Wide, shallow minor groove accessible to proteins.Represents the sodium salt of DNA in a fiber produced at a relative humidity (75%),Diameter (2.3nm),Rise/bp along axis; 2.4 Å (0.24 nm),Inclination of bp to axis +19°. Salwa Hassan Teama
  28. 28. The Z DNA Left-handed helix, Major "groove" not really groove. Narrow minor groove, Its bases seem to zigzag, Diameter (1.8nm), Rise/bp along axis; 3.7 Å (0.37 nm), Inclination of bp to axis; -9°. Salwa Hassan Teama
  29. 29. Salwa Hassan TeamaSource:Phys. Chem. Chem. Phys., 2009,11, 10619-10632
  30. 30. In a solution with higher saltconcentrations or with alcoholadded, the DNA structure maychange to an A form. Salwa Hassan Teama
  31. 31. Salwa Hassan Teama
  32. 32. Semiconservative ReplicationDescribes the method by which DNA isreplicated in all known cells; each strand ofDNA helix serves as a template for the synthesisof complementary DNA strands, it wouldproduce two copies that each contained one ofthe original strands and one entirely new strand. Salwa Hassan Teama
  33. 33. Conservative ReplicationConservative replication;would leave the two originaltemplate DNA strandstogether in a double helix andwould produce a copycomposed of two new strandscontaining all of the newDNA base pairs. Salwa Hassan Teama
  34. 34. Dispersive ReplicationDispersive replication;would produce twocopies of the DNA, bothcontaining distinctregions of DNAcomposed of either bothoriginal strands or bothnew strands. Salwa Hassan Teama
  35. 35. DNA DenaturationWhen a DNA solution is heated enough, thenoncovalent forces that hold the two strands togetherweaken and finally break and the two strand comeapart. Salwa Hassan Teama
  36. 36. Salwa Hassan Teama
  37. 37. Melting TemperatureMelting Temperature; the temperature at which the DNA strandsare half denatured. The GC content of a DNA has a significanteffect on its Tm. The higher a DNA s GC content, the higher itsTm. Salwa Hassan Teama
  38. 38. Relative G+C Contents of Various DNAs Streptococcus pyogenes 34% Haemophilus influenza 39% Escherichia coli 51% Herpes simplex virus 72%Source adapted from: Molecular Biology. Fourth Edition. Robert F. Weaver McGraw-Hill International Edition Salwa Hassan Teama
  39. 39. Salwa Hassan TeamaDenaturation is a reversible process. The two singlecomplementary strands can be made to renaturate or anneal intothe native double stranded molecule by adjusting the temperatureor the salt concentration.
  40. 40. Mitochondrial DNAMitochondrial DNA contains 37 genes, all of which are essentialfor normal mitochondrial function. Thirteen of these genes provide instructions for making enzymes involved in oxidative phosphorylation. The remaining genes provide instructions for making molecules called transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs).Mitochondrial genes are among the estimated 20,000 to 25,000total genes in the human genome. Salwa Hassan Teama
  41. 41. Mitochondrial DNA Salwa Hassan Teama
  42. 42. Salwa Hassan Teama
  43. 43. DNA DamageDNA damage can result from Spontaneous alteration of the DNA molecule during normal cellular processes, such as, DNA replication, DNA repair, or gene rearrangement . Chemical alteration of the DNA molecule itself as a result of hydrolysis, oxidation or methylation. Salwa Hassan Teama
  44. 44. DNA Repair Mechanisms Enzymatic reversal repair Nucleotide excision repair Post-replication repair Salwa Hassan Teama
  45. 45. DNA Repair Salwa Hassan Teama
  46. 46. Recombinant DNARecombinant DNA is DNAthat has been artificiallycreated for purposes ofgenetic engineering. Salwa Hassan Teama
  47. 47. Function of DNA Salwa Hassan TeamaStorage of genetic informationTransmission of genetic information
  48. 48. Genetic engineering Forensic science Bioinformatics DNA nanotechnology ……………… ……..Salwa Hassan Teama
  49. 49. References and Further Reading Ali Khalifa. Applied molecular biology; eds: ( Fathi Tash and Sanna Eissa). 109 pages. Egypt. University Book Center. 2002. Available in paper copy from the publisher Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Molecular Biology of the cell. ISBN. 9780815341055/Available in paper copy from the publisher Daniel H. Farkas. DNA Simplified: The Hitchhikers Guide to DNA. Washington, DC: AACC Press, 1996, ISBN 0-915274-84-1. Available in paper copy from the publisher Franklin R. and Gosling R.G Molecular Configuration in Sodium Thymonucleate. Nature 171, 740-741 (1953). Available in paper copy from the publisher Watson J.D. and Crick F.H.C. A Structure for Deoxyribose Nucleic Acid.. Nature 171, 737-738 (1953). Wilkins M.H.F., A.R. Stokes A.R. & Wilson H.R. Molecular Structure of Deoxypentose Nucleic Acids .Nature 171, 738-740 (1953) Robert F. Weaver. Molecular Biology. Fourth Edition. McGraw-Hill International Edition. ISBN 978-0-07- 110216-2Available in paper copy from the publisher. Robert F. Mueller, Ian D. Young. Emerys Elements of Medical Genetics: ISBN. 044307125X . Available in paper copy from the publisher Salwa Hassan Teama
  50. 50. Salwa Hassan Teama