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DNA Mutations and Repair part 2 and 3

DNA Mutations and Repair part 2 and 3. Chapter 18. Mutation Rates and Frequency. 1 to 10 mutations per million gametes. Incidence within a group. Causes of Mutations. Spontaneous. Induced. Spontaneous. Mispairing of bases Changes in chemical structure of DNA. Tautomers.

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DNA Mutations and Repair part 2 and 3

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  1. DNA Mutations and Repairpart 2 and 3 Chapter 18

  2. Mutation Rates and Frequency 1 to 10 mutations per million gametes Incidence within a group

  3. Causes of Mutations Spontaneous Induced

  4. Spontaneous • Mispairing of bases • Changes in chemical structure of DNA

  5. Tautomers

  6. But this is probably a much more common occurrence. A spontaneous error

  7. Spontaneous Incorporated Error (perhaps due to wobble) To Replicated Errors A replicated Error

  8. Chemical changes to the DNA • Depurination • Deamination

  9. Depurination Chemical change in the DNA

  10. NH2 is gone DNA Repair

  11. Naturally Occurring NO REPAIR!

  12. Environmentally Induced DNA changes

  13. Chemicals and Reactions Leading to Mutations • Base analogs • Alklating agents • Deaminations • Hydroxylamine • Oxidative reactions • Intercalating agents

  14. Mistake!!

  15. alklyating Deamination Adds OH

  16. Oxidative radicals • Reactive forms of oxygen can lead to these radicals

  17. Intercalating agents • Insert and distort DNA

  18. Radiation (Techa River) Hiroshima (Aug. 6th, 1945)

  19. Thymine Dimers SOS

  20. Detecting mutations with the AMES test

  21. THE AMES TEST

  22. AMES TEST • Saccharin • Aflatoxin 2-aminofluorene

  23. Aflatoxin B1

  24. DNA Repair: general characteristics • Double stranded DNA • Redundancy of pathways

  25. Types of DNA repair • Mismatch repair • Direct Repair • Base-Excision Repair • Nucleotide Excision Repair

  26. Mismatch repair • Mut H • Recognize GATC hemi-methylation • Mut S • Mut L

  27. A closer look at mismatch repair

  28. DIRECT REVERSAL REPAIR Direct Repair

  29. BASE EXCISION REPAIR

  30. BASE EXCISION REPAIR

  31. Nucleotide Excision Repair

  32. Diseases of DNA repair!

  33. Xeroderma pigmentosum Autosomal recessive

  34. Hereditary Non-Polyposis Colon Cancer • HNPCC • 15% of all colon cancers

  35. Li-Fraumeni • P-53 mutation

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