Deoxyribophosphate lyase activity of mammalian endonuclease VIII-like proteins.
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.
Grin
Inga R
IR
SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia.
Khodyreva
Svetlana N
SN
Nevinsky
Georgy A
GA
Zharkov
Dmitry O
DO
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
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