Mechanisms of DNA repair

What does base excision repair repair?

• Fixes small, non-helical distortion lesions

• The damage is often oxidative damage (which produces 8-oxofuanine), deamination (deamination of cytosine produces uracil) and alkylation (this can affect base pairing capacity)

What does nucleotide excision repair repair?

• Fixes large, helix distorting lesions

• The damage is often caused by UV agents and mutagens. Could repair thymine dimers and other bulky adducts

Describe the mechanism of base excision repair

• The damaged base is recognised by a DNA glycosylase.

• DNA glycosylase cleaves the glycosidic bond pf the samaged base.

• After the base is removed, the sugar phosphate backbone is cleaved by an AP endonuclease, producing an apurinic/apyrimidinic site

• DNA polymerase then adds the correct base back in, and DNA ligase seals the backbone

Describe the mechanism of nucleotide excision repair

• The helix distortion is recognised and the section of DNA is unwound by TFIIH. A nuclease complex then cuts out the damaged segment

• DNA polymerase then synthesises new nucleotides in the gap

• Gap is sealed by DNA ligase

Compare the lesion sizes between base and nucleotide excision repair

Base excision repair removes single bases or small lesions. Nucleotide excision repair removes larger lesions that cause significant distortions

Describe the complexity of base and nucleotide excision repair

Base excision repair is simple, but nucleotide is much more complex as it requires DNA to be unwound

Describe the occurrences/uses of base and nucleotide excision repair

Base decision repair is often and occurs throughout the cell cycle in order to maintain genome stability, it is part of DNA maintenance.

Nucleotide excision pair is only really active after UV exposure