SET 5 — DNA Damage & Repair

DNA damage

Any chemical or physical change that alters DNA structure or base pairing.

Endogenous DNA damage

Damage that occurs naturally inside cells (e.g., tautomers, depurination, oxidation).

Tautomeric shift

Temporary change in base form that causes mispairing during replication.

Base loss (depurination)

Spontaneous removal of purine base from DNA.

De-amination

Conversion of a base to a different base (e.g., cytosine → uracil).

De-amination of methyl cytosine

Produces thymine; leads to C→T transition if unrepaired.

Oxidative damage

Reactive oxygen species modify bases or break strands.

Replication slippage

Polymerase slips on repetitive sequences, causing insertions or deletions.

Exogenous DNA damage

Damage from external sources like radiation or chemicals.

UV radiation

Causes thymine dimers (covalent link between adjacent thymines).

Ionizing radiation

Causes double-strand breaks or base oxidation.

Consequence of unrepaired DNA damage

Can lead to mutations such as substitutions or indels.

Proofreading

Activity of DNA polymerase that removes mismatched bases during replication.

Base excision repair (BER)

Fixes small, non-helix-distorting base lesions (e.g., deamination, oxidation).

1. Glycosylase

2. AP endonuclease

3. DNA polymerase

4. DNA ligase

Glycosylase

Recognizes and removes damaged base, leaving an abasic (AP) site.

AP endonuclease

Cuts DNA backbone at the abasic site.

DNA polymerase (in BER)

Adds correct nucleotide using complementary base.

DNA ligase (in BER)

Seals the remaining nick in the sugar-phosphate backbone.

Nucleotide excision repair (NER)

Removes bulky distortions such as thymine dimers or chemical adducts.

1. Helicase

2. Endonucleases

3. DNA polymerase

4. DNA ligase

Helicase (in NER)

Unwinds DNA around damaged region.

Endonucleases (in NER)

Cut on both sides of damaged segment.

DNA polymerase (in NER)

Fills the gap with correct nucleotides.

DNA ligase (in NER)

Seals the final phosphodiester bond.

Mismatch repair (MMR)

Fixes mismatched bases that escape proofreading.

1. Endonuclease

2. 5’ exonuclease

3. DNA polymerase

4. DNA ligase

Endonuclease (in MMR)

Cuts near mismatch on new strand.

5’ exonuclease (in MMR)

Removes a stretch of nucleotides containing the error.

DNA polymerase (in MMR)

Refills the gap with correct bases.

DNA ligase (in MMR)

Seals the repaired DNA backbone.

Translesion DNA synthesis

Error-prone DNA polymerase

Nonhomologous end joining (NHEJ)

Directly joins double-strand break ends, often causing small insertions or deletions.

Homologous recombination (HR)

Uses homologous DNA sequence as template for accurate repair of double-strand breaks.

Enzyme types used in repair

Include glycosylase, endonuclease, exonuclease, DNA polymerase, ligase, and helicase.

Mutation if repair fails

DNA damage that isn’t fixed can cause substitution or frameshift mutations.