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| Subject Categories: Genome Stability & Dynamics | Structural Biology |
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| The EMBO Journal
(2007) 26, 2206–2217, doi:10.1038/sj.emboj.7601662 Published online 29 March 2007 |
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| Structural basis for enzymatic excision of N1-methyladenine and N3-methylcytosine from DNA |
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| Ingar Leiros1, 5, Marivi P Nabong2, 3, 5, Kristin Grøsvik3, Jeanette Ringvoll2, Gyri T Haugland4, Lene Uldal2, Karen Reite2, Inger K Olsbu3, Ingeborg Knævelsrud3, 4, Elin Moe1, Ole A Andersen1, Nils-Kåre Birkeland4, Peter Ruoff3, Arne Klungland2 and Svein Bjelland3 |
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1 The Norwegian Structural Biology Centre, University of Tromsø, Tromsø, Norway 2 Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, University of Oslo, Rikshospitalelt-Radiumhospitalet HF, Oslo, Norway 3 Faculty of Science and Technology, Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway 4 Department of Biology, University of Bergen, Bergen, Norway To whom correspondence should be addressed Svein Bjelland, Faculty of Science and Technology, Department of Mathematics and Natural Sciences, University of Stavanger, Kristine Bonnevies rd 30, N-4036 Stavanger, Norway. Tel.: +47 51831884; Fax: +47 51831750; E-mail: svein.bjelland@uis.no 5 These authors contributed equally to this work Received 11 August 2006; Accepted 1 March 2007; Published online 29 March 2007. |
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| Abstract |
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| N1-methyladenine (m1A) and N3-methylcytosine (m3C) are major toxic and mutagenic lesions induced by alkylation in single-stranded DNA. In bacteria and mammals, m1A and m3C were recently shown to be repaired by AlkB-mediated oxidative demethylation, a direct DNA damage reversal mechanism. No AlkB gene homologues have been identified in Archaea. We report that m1A and m3C are repaired by the AfAlkA base excision repair glycosylase of Archaeoglobus fulgidus, suggesting a different repair mechanism for these lesions in the third domain of life. In addition, AfAlkA was found to effect a robust excision of 1,N6-ethenoadenine. We present a high-resolution crystal structure of AfAlkA, which, together with the characterization of several site-directed mutants, forms a molecular rationalization for the newly discovered base excision activity. |
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| Keywords: AlkA, Archaeoglobus fulgidus , DNA repair, 1-methyladenine, 3-methylcytosine |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHStructural basis for enzymatic excision of N 1 -methyladenine and N 3 -methylcytosine from DNA The EMBO Journal Article DNA damage recognition and repair by 3-methyladenine DNA glycosylase I (TAG) The EMBO Journal Article DNA damage recognition and repair by 3-methyladenine DNA glycosylase I (TAG) The EMBO Journal Article (02 May 2007) Crystal structures of 3-methyladenine DNA glycosylase MagIII and the recognition of alkylated bases The EMBO Journal Article (01 Oct 2003) |
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