Excision of a lyase-resistant oxidized abasic lesion from DNA

The C2'-oxidized abasic lesion (C2-AP) is produced in DNA that is subjected to oxidative stress. The lesion disrupts replication and gives rise to mutations that are dependent upon the identity of the upstream nucleotide. Ape1 incises C2-AP, but the 5'-phosphorylated fragment is not a substrate for the lyase activity of DNA polymerase beta. Excision of the lesion is achieved by strand displacement synthesis in the presence of flap endonuclease during which C2-AP and the 3'-adjacent nucleotide are replaced. The oxidized abasic lesion is also a substrate for the bacterial UvrABC nucleotide excision repair system. These data suggest that the redundant nature of DNA repair systems provides a means for removing a lesion that resists excision by short patch base excision repair.