Figure 5.

Repair of oxidative DNA damage introduces genome heterogeneity and instability. ROS causes oxidation of DNA bases which then elicit base excision repair machineries. First, the oxidized base is cleaved by glycosylase leaving an apurinic/apyrimidinic site (AP site). Second, the AP site is recognized by AP endonuclease that cleaves the phosphodiester bonds to remove the AP nucleotide and create the single-strand break (SSB) intermediate. DNA polymerase then resynthesizes the missing part of the DNA and later DNA ligase seals the nick. The low fidelity of the translesion DNA polymerase increases the chance of mismatched base-pairing and thus, leads to accumulation of point mutations which creates genome heterogeneity.