DNA repair mechanisms

Mismatch Repair

methylation directed, repairs abnormally paired (mismatched, G with T) bases

Base Excision Repair

Spontaneous deamination (removes damaged single bases)

Nucleotide excision repair

Thymine dimers (DNA lesions - multibase)

Sit-Specific Repair

removes modified bases

MMR mechanism

1. DAM methylation carried out by DAM methyltranserase —> methylation of A residues in GATC sequences

2. newly synthesized DNA is briefly not methylated (hemimethylated)

3. methylation marks newly synthesized DNA for repair

4. MutH binds at the hemimethylated A

5. MutS and MutL bind together and move along DNA until they find mutH

6. MutH then cleaves the unmethylated strand at hemi-methylated site

7. Exonucleases remove newly synthesized DNA btw the mismatched DNA and the cleaved site

8. DNA pol III resynthesizes DNA

9. Ligase seals

BER mechanism

most common damage is cytosine damaged to uracil —> damaged means they no longer resemble their base identity

1. DNA glycosylase removes the damaged base—> abasic site

2. AP endonuclease recognizes abasic sites and nicks the phosphate backbone

3. DNA pol 1 fills in the damaged DNA

4. DNA ligase connects back together

NER mechanism

Repair of multi-base lesions (thymine dimers)

1. Excinuclease nicks both sides of lesion

2. DNA helicase unwinds DNA around the lesion —→ 3’ OH and 5’ P

3. DNA pol 1 fills removed DNA

4. DNA ligase connects everything back together

Direct repair mechanism

Repairs modified bases — still have base identity but another funct. group is added

— usually methylation, red/ox of alcohols and aldehydes, they base pair with wrong thing and cause mutations if the strand it pairs with becomes a template

1. O6-methylguananine abnormally pairs with T

2. methyltransferases remove methyl group with no nich —> then permanently inactivated

3. covalently bind to the DNA

SOS repair in ECOLI

Stops DNA replication until recombination removes the lesion

error prone repair takes over —> replicates with wrong bases anyway but its better than not replicating and dying)