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Nucleic Acids Research 2005 33(15):4849-4856; doi:10.1093/nar/gki816
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Published online 29 August 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org


Article

NEIL1 excises 3' end proximal oxidative DNA lesions resistant to cleavage by NTH1 and OGG1

Jason L. Parsons, Dmitry O. Zharkov1 and Grigory L. Dianov*

MRC Radiation and Genome Stability Unit Harwell, Oxfordshire, OX11 0RD, UK 1SB RAS Institute of Chemical Biology and Fundamental Medicine Novosibirsk 630090, Russia

*To whom correspondence should be addressed. Tel: +44 1235 841 134; Fax: +44 1235 841 200; Email: g.dianov{at}har.mrc.ac.uk

Received July 22, 2005. Revised August 18, 2005. Accepted August 18, 2005.

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.


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