The role of mammalian NEIL1 protein in the repair of 8-oxo-7,8-dihydroadenine in DNA |
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| Authors: | Inga R Grin Dmitry O Zharkov |
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| Institution: | a SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., Novosibirsk 630090, Russia
b Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK |
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| Abstract: | 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. |
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| Keywords: | BER base excision repair LIG3α DNA ligase IIIα NEIL1 endonuclease VIII-like protein 1 OGG1 8-oxoguanine-DNA-glycosylase 1 PNKP polynucleotide kinase/3&prime -phosphatase POLβ DNA polymerase β |
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