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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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DNA Glycosylases / genetics
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DNA Glycosylases / metabolism*
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DNA Polymerase beta / metabolism
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DNA Repair
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DNA-Formamidopyrimidine Glycosylase / genetics
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Deoxyribonuclease (Pyrimidine Dimer) / genetics
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Deoxyribonuclease (Pyrimidine Dimer) / metabolism*
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Escherichia coli Proteins / genetics
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Humans
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Molecular Sequence Data
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Molecular Structure
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Nucleic Acid Conformation
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Phosphorus-Oxygen Lyases / metabolism*
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Sequence Alignment
Substances
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Escherichia coli Proteins
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5'-deoxyribose phosphate lyase
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DNA Polymerase beta
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Deoxyribonuclease (Pyrimidine Dimer)
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Nei protein, E coli
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DNA Glycosylases
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Neil1 protein, mouse
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Neil2 protein, mouse
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DNA-Formamidopyrimidine Glycosylase
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DNA-formamidopyrimidine glycosylase, E coli
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Phosphorus-Oxygen Lyases