Human DNA polymerase β initiates DNA synthesis during long-patch repair of reduced AP sites in DNA

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Abstract
Simple base damages are repaired through a short‐patch base excision pathway where a single damaged nucleotide is removed and replaced. DNA polymerase β (Pol β) is responsible for the repair synthesis in this pathway and also removes a 5′‐sugar phosphate residue by catalyzing a β‐elimination reaction. How ever, some DNA lesions that render deoxyribose resistant to β‐elimination are removed through a long‐patch repair pathway that involves strand displacement synthesis and removal of the generated flap by specific endonuclease. Three human DNA polymerases (Pol β, Pol δ and Pol ϵ) have been proposed to play a role in this pathway, however the identity of the polymerase involved and the polymerase selection mechanism are not clear. In repair reactions catalyzed by cell extracts we have used a substrate containing a reduced apurinic/apyrimidinic (AP) site resistant to β‐elimination and inhibitors that selectively affect different DNA polymerases. Using this approach we find that in human cell extracts Pol β is the major DNA polymerase incorporating the first nucleotide during repair of reduced AP sites, thus initiating long‐patch base excision repair synthesis.