Deoxyribophosphate lyase activity of mammalian endonuclease VIII-like proteins

AbstractBase 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