Deoxyribophosphate lyase activity of mammalian endonuclease VIII‐like proteins

Abstract

Base excision repair (BER) protects cells from nucleobase DNA damage. In eukaryotic BER, DNA glycosylases generate abasic sites, which are then converted to deoxyribo‐5′‐phosphate (dRP) and excised by a dRP lyase (dRPase) activity of DNA polymerase β (Polβ). Here, we demonstrate that NEIL1 and NEIL2, mammalian homologs of bacterial endonuclease VIII, excise dRP by β‐elimination with the efficiency similar to Polβ. DNA duplexes imitating BER intermediates after insertion of a single nucleotide were better substrates. NEIL1 and NEIL2 supplied dRPase activity in BER reconstituted with dRPase‐null Polβ. Our results suggest a role for NEILs as backup dRPases in mammalian cells.