Dna damage and repair

DNA damage and repair

uploaded by Abbas W Abbas

NA Damage andRepair

By : Ayah Tuffaha

Supervisor : Dr. Mustafa Ghanim

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

DNA DamageDna 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

Repair Mechanisms

• Translesion Synthesis

• Excision Repair

• Mismatch Repair

• Double Strand Break Repair Mechanisms

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.

Excision Repair

3 Step Process“Cut and Patch”

Each step requires a specific enzyme1-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 process3- DNA Ligase form phosphoester bond between repaired strand and newly

synthesized nucleotides

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.

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.

Why doesn’t DNA contain any Uracil?

Deamination of cytosine gives uracilSo 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.

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