DNA Damage and repair

1. -Akshay More

2. Natural polymerase error
Endogenous DNA damage
-oxidative damage
-depurination
Exogenous DNA damage
-radiation
-chemical adducts

3. A)Base Substitutions:
1) Transition
5`-G-C-A-C- 3` Mutation 5`-G-C-G-C-3`
3`-C-G-T-G- 5` 3`-C-G-C-G-5`
2) Transversion
5`-G-C-A-C-3` Mutation 5` -G-C-T-C- 3`
3`-C-G-T-G- 5` 3` -C-G-A-G- 5`
B) Frameshift Mutations:
1) Insertion
5`-G-C-A-C-3` Mutation 5` -G-C-A-T-C-3`
3`-C-G-T-G- 5` 3` -C-G-T-A-G-5`
2) Deletion
5`-G-C-A-C-3` Mutation 5`-G-C-C-3`
3`-C-G-T-G- 5` 3`-C-G-G-5`

4. 1) Photo-reactivation
-Only in bacteria.
-Photolyase enzyme.
-Activates by visible light (320-370 nm).
-Cleaves Thiamine Dimers.
2) Base excision repair (BER)
 Major pathway for repair of modified bases, uracil mis-
incorporation, oxidative damage
 Various DNA glycosylases recognize lesion and remove
base at glycosidic bond, thereby producing an “abasic” or AP
(apurinic/ apyrimidinic) site by base “flipping out”.
 One of several AP endonucleases incises
phosphodiesterase backbone adjacent to AP site
 AP nucleotide removed by exonuclease/dRPase and patch
refilled by DNA synthesis and ligation

7.  Under normal conditions:
-Gene lex A -> lex A protein.
-lex A binds to promoter of genes coding repair enzymes.
-Repair enzymes not synthesized.
 If mutation occurs:
-SOS System activated.
-rec A gene -> rec A protein.
- Signal + rec A protein = protease
- Protease cleaves lex A
- Promoter become free.
- Repair enzymes synthesized.

8. SOS repair in E. coli

9. THANK
YOU