1. DNA Mutations and Repair
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. Mustard Gas: alkylating agent

17. Oxidative radicals
Reactive forms of oxygen can lead to these radicals

18. Intercalating agents
Insert and distort DNA

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

20. Thymine Dimers
SOS

21. Detecting mutations with the AMES test

23. THE AMES TEST

24. AMES TEST
Saccharin
Aflatoxin
2-aminofluorene

25. Aflatoxin B1

26. DNA Repair: general characteristics
Double stranded DNA
Redundancy of pathways

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

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

29. A closer look at mismatch repair

30. DIRECT REVERSAL REPAIR
Direct Repair

31. BASE EXCISION REPAIR

32. BASE EXCISION REPAIR

33. Nucleotide Excision Repair

34. Diseases of DNA repair!

35. Xeroderma pigmentosum
Autosomal recessive

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

37. Li-Fraumeni
P-53 mutation