Cellular DNA Repair of Oxidative Deoxyribose Damage by Mammalian Long-Patch Base Excision Repair

2-Deoxyribonolactone (dL) arises as a major DNA damage induced by a variety of agents, involving free radical attack and oxidation of Cl'-deoxyribose in DNA. We investigated whether dL lesions can be repaired in mammalian cells and the mechanisms underlying the role of DNA polymerase β in processing of dL lesions. Pol β appeared to be trapped by dL residues, resulting in stable DNA-protein cross-links. However, repair DNA synthesis at site-specific dL sites occurred effectively in cell-free extracts, but predominantly accompanied by long-patch base excision repair (BER) pathway. Reconstitution of long-patch BER demonstrated that FEN1 was capable of removing the displaced flap DNA containing a 5'-dL residue. Cellular repair of dL lesions was largely dependent on the DNA polymerase activity of Pol β. Our observations reveal repair mechanisms of dL and define how mammalian cells prevent cytotoxic effects of oxidative DNA lesions that may threaten the genetic integrity of DNA.