The role of mammalian NEIL1 protein in the repair of 8-oxo-7,8-dihydroadenine in DNA.
8-oxo-7,8-dihydroadenine (8-oxoAde) is a major product of adenine modification by reactive oxygen species. So far, only one mammalian DNA glycosylase, 8-oxoguanine-DNA-glycosylase 1 (OGG1), has been shown to excise 8-oxoAde, exclusively from pairs with Cyt. We have found that endonuclease VIII-like protein 1 (NEIL1), a mammalian homolog of bacterial endonuclease VIII, can efficiently remove 8-oxoAde from 8-oxoAde:Cyt pairs but not from other contexts. In an in vitro reconstituted system, reactions containing OGG1 produced a fully repaired product, whereas NEIL1 caused an abortive initiation of repair, stopping after 8-oxoAde removal and DNA strand cleavage. This block was partially relieved by polynucleotide kinase/3'-phosphatase. Thus, two alternative routes of 8-oxoAde repair may exist in mammals.
Grin
Inga R
IR
SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia.
Dianov
Grigory L
GL
Zharkov
Dmitry O
DO
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D020137:Base Pair Mismatch; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D007700:Kinetics; D051379:Mice
C002992:8-hydroxyadenine; D004247:DNA; D045647:DNA Glycosylases; D000225:Adenine