DNA can be damaged through spontaneous interactions with water molecules, exposure to mutagens like radiation or chemicals, or during DNA replication if a wrong nucleotide is incorporated. There are several DNA repair mechanisms to fix damage: translesion synthesis tolerates damage by replicating past it; excision repair cuts out the damaged section and replaces it with the correct nucleotides; mismatch repair fixes improperly paired bases; and double-strand break repair mechanisms like non-homologous end joining or homologous recombination are used to repair breaks in both strands of DNA. The cell can determine the correct nucleotide sequence using the newly synthesized strand as a guide since it contains the wrongly incorporated base.

1. DNA damage and repair
uploaded by Abbas W Abbas

2. D Repair
and
NA
amage
By : Ayah Tuffaha
Supervisor : Dr. Mustafa Ghanim

3. DNA Damage vs. DNA Mutation
• Physical abnormalities or • Change in normal
abnormal chemical nucleotide sequence in
modifications DNA
• Cannot be inherited • Can be inherited
• Effects :Prevents
replication and
transcription or may cause
mutation if damaged DNA
is replicated

4. DNA Damage
Dna Damage occurs:
•
Spontaneously
Interactions with water molecules causing hydrolysis of bonds
–
Deamination
–
Depurination
•
Mutagens
–
Radiation e.g. UV
Causes pyrimidine dimers
–
Chemicals e.g. base
analogs, base
modifying
agents(DNA
adducts),
intercalating agents

6. Repair Mechanisms
•
Translesion Synthesis
•
Excision Repair
•
Mismatch Repair
•
Double Strand Break Repair
Mechanisms

7. Translesion Synthesis
Damage Tolerance Mechanism
Original DNA strand is still damaged but the newly synthesized DNA strand
is normal.
Specialized DNA polymerase
synthesizes DNA across regions in
which DNA template is damaged

8. Excision Repair
3 Step Process
“Cut and Patch”
Each step requires a specific enzyme
1-Removal of defective nucleotides via endonuclease
The phosphoester bonds on both sides of the damaged location are broken
by the endonuclease and it removed by exonuclease or DNA helicase
2-The missing nucleotides are replaced with the correct ones by a DNA
polymerase
Other DNA strand is used as a template during the process
3- DNA Ligase form phosphoester bond between repaired strand and newly
synthesized nucleotides

10. Excision Repair
There are two types :
•
Base excision: Single damaged base
e.g. Deaminated base -> DNA glycosylase
Deaminated base is removed via glycosylase leaving behind ribose phosphate on
DNA strand and sugar ribose is then removed via excision process.
•
Nucleotide excision (NER): Multiple base
damage
Transcription coupled repair
When transcription stops because of DNA damage the NER is recruited to that damaged
location and this process speeds up the repairing process for ACTIVE GENES.

11. Mismatch Repair
•
Wrong base pairing e.g. A with C
•
Improper hydrogen bonding
Also “Cut and Patch” like excision and nearly the same mechanism(3 step removal process).
Differs in type of abnormality repaired because here the nucleotides are normal (not abnormal
like excision) but they have been improperly paired during replication.
How does the cell recognize which is the
wrong nucleotide?
How is that nucleotide removed?
The cell recognizes the nucleotide that should be removed by recognizing the newly
synthesized strand from the original strand. The newly synthesized strand is
the one that has the wrongly incorporated nucleotide.

12. Why doesn’t DNA
contain any Uracil?
Deamination of cytosine gives uracil
So if uracil was normally present in DNA the repair system will NOT be able to recognize
the normally present uracil from the abnormally present uracil and therefore
won’t be able to repair the damage caused.

13. Double-Strand DNA Breaks
•
DNA helix is broken to two fragments
•
Repair Mechanisms:
•
Non-homologous end joining : error prone
Repairs the break without template
•
Homologous recombination
Uses homologous chromosome (All chromosome are present as homologous pairs) as template