Structural basis for enzymatic excision of N super(1)-methyladenine and N super(3)-methylcytosine from DNA

N super(1)-methyladenine (m super(1)A) and N super(3)-methylcytosine (m super(3)C) are major toxic and mutagenic lesions induced by alkylation in single-stranded DNA. In bacteria and mammals, m super(1)A and m super(3)C were recently shown to be repaired by AlkB-mediated oxidative demethylation, a d...

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Published in:The EMBO journal 2007-01, Vol.26 (8), p.2206-2217
Main Authors: Leiros, Ingar, Nabong, Marivi P, Groesvik, Kristin, Ringvoll, Jeanette, Haugland, Gyri T, Uldal, Lene, Reite, Karen, Olsbu, Inger K, Knaevelsrud, Ingeborg, Moe, Elin, Andersen, Ole A, Birkeland, Nils-Kaare, Ruoff, Peter, Klungland, Arne, Bjelland, Svein
Format: Article
Language:English
Subjects:
Archaea
Archaeoglobus fulgidus
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Summary:N super(1)-methyladenine (m super(1)A) and N super(3)-methylcytosine (m super(3)C) are major toxic and mutagenic lesions induced by alkylation in single-stranded DNA. In bacteria and mammals, m super(1)A and m super(3)C 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 m super(1)A and m super(3)C 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,N super(6)-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.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601662