Purification and characterization of NEIL1 and NEIL2, members of a distinct family of mammalian DNA glycosylases for repair of oxidized bases.

NEIL1 and NEIL2 were newly discovered as mammalian orthologs of Escherichia coli Nei and Fpg, oxidized base-specific DNA glycosylases. These are distinct from previously characterized OGG1 and NTH1, the other two glycosylases for repairing oxidatively damaged bases in mammalian cells, in regards to reaction mechanism. Recombinant human NEIL1 and NEIL2 were purified from E. coli and biochemically characterized. Some damaged bases are common substrates for both groups of enzymes. However, in contrast to the lack of activity of NTH1 and OGG1 for substrate lesions in single-stranded DNA, the NEILs have unique preference for bubble or single-stranded DNA substrates, suggesting their preferential involvement in repairing transcribed or replicating DNA sequences.