1. Mutation Point Mutations Spontaneous Induced Depurination Deamination
Oxidatitive damage
Replication errors
Trinucleotide repeat expansion and human disease
Induced
Base analogs
Base modifiers
Base damagers (DNA damage)
Ames Test for Mutagens (because some mutagens = carcinogens)

2. Spontaneous Mutations: Depurination

3. Depurination: Mutagenesis by SOS-mediated repair

4. Spontaneous Deamination: Cytosine to Thymine
5 methyl C’s
Are hot spots
For mutations

5. Spontaneous Mutations: Oxidative damage
G-C to T-A transversions

6. Spontaneous Replication Errors: Amino to Imino Cytosine
G-C to A-T and A-T to G-C transitions

7. Spontaneous Replication Errors: Keto to Enol Thymine
A-T to G-C and G-C to A-T transitions

8. Spontaneous Replication Errors: Amino to Imino Adenine
A-T to G-C and G-C to A-T transitions

9. Spontaneous Replication Errors: Keto to Enol Guanine
G-C to A-T and A-T to G-C transitions

12. Spontaneous INDEL Mutations: insertion or deletion of one to a few bps
Slippage and mispairing in repeat-rich sequences
“hot spots” for indel mutations

13. Trinucleotide Repeat Expansions: Fragile-X syndrome

14. Induced Mutations: Base Analogs: 5 BU (5BrdU)

15. Induced Mutations: Base Analogs: 2-AP (2 aminopurine)

16. Induced Mutations: Base Modifiers: EMS and NG (ethylmethansulfonate and nitrosoquanidine)

17. Induced Mutations: Intercalating Drugs (intercalating dyes)

18. Induced Mutations: UV Light

19. Experimental Test for Mutagens: the Ames Test

20. Induced Mutations: AFB1 and G-C to T-A transversions

21. Example Results of the Ames Test
TA100: requires a missense
TA1538: requires a frame shift

22. Summary of Spontaneous and Induced Mutations
Imino C pairs with A: G-C to A-T transition
A-T to G-C
Enol T pairs with G: A-T to G-C
G-C to A-T
Imino A pairs with C: A-T to G-C
Enol G pairs with T: G-C to A-T
Ionized 5 BU pairs with G: A-T to G-C
Protonated 2-AP pairs with C: A-T to G-C
0-6 ethyl guanine pairs with T G-C to A-T
Aflatoxin-mediated depurination of G: G-C to T-A transversion