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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.

Original publication

DOI

10.1016/j.febslet.2010.03.009

Type

Journal article

Journal

FEBS Lett

Publication Date

16/04/2010

Volume

584

Pages

1553 - 1557

Keywords

Adenine, Animals, Base Pair Mismatch, Base Sequence, DNA, DNA Glycosylases, DNA Repair, Humans, Kinetics, Mice