title: 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 beta (Polbeta). Here, we demonstrate that NEIL1 and NEIL2, mammalian homologs of bacterial endonuclease VIII, excise dRP by beta-elimination with the efficiency similar to Polbeta. 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 Polbeta. Our results suggest a role for NEILs as backup dRPases in mammalian cells.
authors.affiliation: SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia.
authors.forename: Inga R
authors.initials: IR
authors.lastname: Grin
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Khodyreva
authors.forename: Georgy A
authors.initials: GA
authors.lastname: Nevinsky
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Zharkov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase / Q000235:genetics; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D019761:Phosphorus-Oxygen Lyases / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D029968:Escherichia coli Proteins; C423906:5'-deoxyribose phosphate lyase; D019951:DNA Polymerase beta; D043224:Deoxyribonuclease (Pyrimidine Dimer); C468346:Nei protein, E coli; D045647:DNA Glycosylases; C481347:Neil1 protein, mouse; C502613:Neil2 protein, mouse; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; D019761:Phosphorus-Oxygen Lyases