Dna damage and repair

this presentation presented by Ayah Tuffaha about dna damage and repair

1. DNA damage and repair
uploaded by Abbas W Abbas

2. NA Damage
andRepair



By : Ayah Tuffaha
Supervisor : Dr. Mustafa Ghanim

3. DNA Damage vs. DNA Mutation

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

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

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

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

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
•
Nucleotide excision (NER): Multiple base
damage
Transcription coupled repair
Deaminated base is removed via glycosylase leaving behind ribose phosphate on
DNA strand and sugar ribose is then removed via excision process.
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
How does the cell recognize which is the
wrong nucleotide?
How is that nucleotide removed?
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.
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
•
Homologous recombination
Repairs the break without template
Uses homologous chromosome (All chromosome are present as homologous pairs) as template