The role of mammalian NEIL1 protein in the repair of 8-oxo-7,8-dihydroadenine in DNA

Edited by Barry Halliwell

Received 4 February 2010; received in revised form 4 March 2010; accepted 4 March 2010. published online 08 March 2010.

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.

Abbreviations: BER, base excision repair, LIG3α, DNA ligase IIIα, NEIL1, endonuclease VIII-like protein 1, OGG1, 8-oxoguanine-DNA-glycosylase 1, PNKP, polynucleotide kinase/3′-phosphatase, POLβ, DNA polymerase β

Keywords: DNA repair, DNA glycosylase, Endonuclease VIII homolog, 8-Oxoadenine

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

Corresponding author. Fax: +7 383 3333677.

PII: S0014-5793(10)00203-6

doi:10.1016/j.febslet.2010.03.009

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