1. The Damage and Repair of DNA The molecular basis of point mutations 1. Base substitution (mismatches) transition transversion Two main types of DNA damage: *point mutations *structural changes 2. Tautomeric shift

2. 3. Base analogs and chemical mutagens Gene Mutation The molecular basis of point mutations

3. DNA Damage The molecular basis of structural damage 1. Hydrolytic damage N-glycosidic bond – very weak and easily broken Deamination Depurination

4. DNA Damage The molecular basis of structural damage 2. Alkylation

5. DNA Damage The molecular basis of structural damage 3. Oxidation and Radiation

6. Repairing Damages Bases 1. Mismatch repair (MMR) Dam methylase:MutS:

7. 1. Mismatch repair (MMR) Repairing Damages Bases

8. 2. Photoreactivation Repairing Damages Bases

9. 3. Repair of alkylation Repairing Damages Bases

10. 4. Base excision repair (BER) (BER) Repairing Damages Bases

11. 4. Base excision repair (BER) Repairing Damages Bases

12. 5. Nucleotide excision repair (NER) Repairing Damages Bases

13. DNA Repair 7. Double Strand Break Repair (DSB) Nonhomologous End-Joining (NHEJ) Ku XRCC4 DNA-PK cs Artemis Ligase

14. DNA Repair 8. Double Strand Break (DSB) repair (Homologous Recombination)

15. DNA Repair 8. Double Strand Break (DSB) repair (Homologous Recombination)