DNA Repair system

2. DNA Repair
• To maintain the genetic stability .
Damage / Mutation
Lesion
Repair genetic material
To maintain essential cellular function

3. Direct Repair system
• Repaired by light dependent direct system—Photoreactivation
DNA photolyase= 300-500 nm light= Active.
T=T (Thymine=Thymine Dimer) ---------- T T Normal

4. Repair system
Direct Repair
1) Photoreactivation
Excision Repair
BER
NER
Mismatch
Transcriptional coupled
repair system
Double stranded
Break Repair
Homologous
recombination
Non-homologous
End joining Mech:
Single stranded DNA Repair
(Translession DNA Synthesis)

5. BER-Base Excision Repair
1. DNA glycosylase – Initiate the Repair process.
Does not break phosphodiester bond.
Cleave only N-glycosidic bond and generating
Apurinic or Apyrimidinic site called as AP Site..
2. AP Endonuclease- cleave DNA Backbone 5’ to the
AP site.
3. DNA Polymearase replace the missing nucleotides
4. DNA Ligase - subsequent rejoining of the
phosphodiester backbone

6. NER -
• Breaking of a phosphodiester bond on either side of lesion on
same strand.
• Excision of oligo-nucleotides.
1. Uvr-A,B,C = ABC Excinuclease Binds to DNA at the site of
lesion
2.Uvr-A and B attach DNA at damage site.
3.Uvr-A recognize damage site and allows Uvr-C to forming Uvr B-
C dimer.
4.Uvr B-C dimer – cleave damage strand upto eighth
phosphodiester bond on the 5’ site of lesion and upto fourth
phosphodiester bond at 3’ site.
DNA Pol - Gap fill
DNA Ligase gap sealed.
Xeroderma pigmantosum and cockayane syndrome are caused by
genetically defective NER.
Inability of skin cells to repair UV induced DNA lesions (Pyrimidine
dimer)
Sensitive to sunlight...

7. Transcription coupled repair system:
• It works during Transcription process.
• Found in both Prokaryotic = TRCF( transcription factor F) and Eukaryotic =
TF2H (transcription factor-II-H)
• When RNA pol slips or DNA damage during transcription process, TRCF
and TF2H recruits at damage site in Prokaryotic and Eukaryotic
respectively.
• Then NER system repairs the damage.
• If mutation occur in TCR system cockayane syndrome occurs.

8. Mismatch Repair System
1. DNA Polymerase Slippage error.
2. Replication Machinery = Error correct
3. Work in S Phase also work after replication
compilated
prokaryotic
Mut H: Recognize Hemi-Methylated DNA,Endonuclease
Mut L: Mediate between MutS and MutH
Mut S: Recognize Mis-Match.
1. GATC Sequence are Hemi-methylated
during Replication, methylation at A on
parental strand.
2. Mut S once recognize the mis-match via
Mut L it induce endonuclease activity
Mut H.
3. Gap fill by DNA poly III and Nick sealing by
DNA Ligase

9. Mismatch Repair System
• Eukaryotic
• Mut Homologue Protein
• Recognize mismatch = MSH
• Mut L Homologue (MLH)- Endonuclease Activity
• There is no Mut H homologue protein in euk system
• No Hemimethylated Condition
• Reorganization of parental /new strand is based on presence of okazakki
fragments.
• Mutation in Mismatch repair system causes Colon cancer.

10. Thank You……
??????????