Deoxyribophosphate lyase activity of mammalian endonuclease VIII-like proteins

FEBS Lett. 2006 Sep 4;580(20):4916-22. doi: 10.1016/j.febslet.2006.08.011. Epub 2006 Aug 15.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism*
  • DNA Polymerase beta / metabolism
  • DNA Repair
  • DNA-Formamidopyrimidine Glycosylase / genetics
  • Deoxyribonuclease (Pyrimidine Dimer) / genetics
  • Deoxyribonuclease (Pyrimidine Dimer) / metabolism*
  • Escherichia coli Proteins / genetics
  • Humans
  • Molecular Sequence Data
  • Molecular Structure
  • Nucleic Acid Conformation
  • Phosphorus-Oxygen Lyases / metabolism*
  • Sequence Alignment


  • Escherichia coli Proteins
  • 5'-deoxyribose phosphate lyase
  • DNA Polymerase beta
  • Deoxyribonuclease (Pyrimidine Dimer)
  • Nei protein, E coli
  • DNA Glycosylases
  • Neil1 protein, mouse
  • Neil2 protein, mouse
  • DNA-Formamidopyrimidine Glycosylase
  • DNA-formamidopyrimidine glycosylase, E coli
  • Phosphorus-Oxygen Lyases