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

3. Base analogs and chemical mutagens

Gene MutationThe molecular basis of point mutations

DNA DamageThe molecular basis of structural damage

1. Hydrolytic damage

N-glycosidic bond – very weak and easily broken

Deamination

Deamination

Depurination

DNA DamageThe molecular basis of structural damage

2. Alkylation

DNA DamageThe molecular basis of structural damage

3. Oxidation and Radiation

Repairing Damages Bases

1. Mismatch repair (MMR)

Dam methylase: MutS:

1. Mismatch repair (MMR)

Repairing Damages Bases

2. Photoreactivation

Repairing Damages Bases

3. Repair of alkylation

Repairing Damages Bases

4. Base excision repair (BER)

(BER)Repairing Damages Bases

4. Base excision repair (BER)

Repairing Damages Bases

5. Nucleotide excision repair (NER)

Repairing Damages Bases

DNA Repair

7. Double Strand Break Repair (DSB)

Nonhomologous End-Joining (NHEJ)

Ku

XRCC4

DNA-PKcs

Artemis

Ligase

DNA Repair

8. Double Strand Break (DSB) repair (Homologous Recombination)

DNA Repair8. Double Strand Break (DSB) repair (Homologous Recombination)