title: NEIL1 excises 3' end proximal oxidative DNA lesions resistant to cleavage by NTH1 and OGG1.
abstract: Base excision repair is the major pathway for the repair of oxidative DNA damage in human cells that is initiated by a damage-specific DNA glycosylase. In human cells, the major DNA glycosylases for the excision of oxidative base damage are OGG1 and NTH1 that excise 8-oxoguanine and oxidative pyrimidines, respectively. We find that both enzymes have limited activity on DNA lesions located in the vicinity of the 3' end of a DNA single-strand break, suggesting that other enzymes are involved in the processing of such lesions. In this study, we identify and characterize NEIL1 as a major DNA glycosylase that excises oxidative base damage located in close proximity to the 3' end of a DNA single-strand break.
authors.affiliation: MRC Radiation and Genome Stability Unit Harwell, Oxfordshire, OX11 0RD, UK.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Parsons
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Zharkov
authors.forename: Grigory L
authors.initials: GL
authors.lastname: Dianov
mesh_terms: D001483:Base Sequence; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress; D013379:Substrate Specificity; D014498:Uracil / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D009841:Oligonucleotides; C045975:5-hydroxyuracil; C024829:8-hydroxyguanine; D014498:Uracil; D006147:Guanine; D043224:Deoxyribonuclease (Pyrimidine Dimer); C468347:NTHL1 protein, human; D045647:DNA Glycosylases; C473634:NEIL1 protein, human; C479058:oxoguanine glycosylase 1, human