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Significance Oxidative DNA damage has been postulated to play an important role in human neurodegenerative disorders and cancer. 8,5′-cyclo -2′-deoxyadenosine (cdA) is generated in DNA by hydroxyl radical attack and strongly blocks DNA replication and transcription. Here we demonstrate that cdA adducts at 3′ termini of DNA can be removed by 3′-5′ exonuclease activity of the apurinic/apyrimidinic (AP) endonucleases:Escherichia coli Xth and human APE1. The crystal structure of bacterial AP endonuclease in complex with DNA duplex provides insight into the mechanism of this activity. This new repair function provides an alternative pathway to counteract genotoxic effect of helix-distorting DNA lesions.

Insight into mechanisms of 3′-5′ exonuclease activity and removal of bulky 8,5′-cyclopurine adducts by apurinic/apyrimidinic endonucleases