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Structural basis for enzymatic excision of N 1 ‐methyladenine and N 3 ‐methylcytosine from DNA
Author(s) -
Leiros Ingar,
Nabong Marivi P,
Grøsvik Kristin,
Ringvoll Jeanette,
Haugland Gyri T,
Uldal Lene,
Reite Karen,
Olsbu Inger K,
Knævelsrud Ingeborg,
Moe Elin,
Andersen Ole A,
Birkeland NilsKåre,
Ruoff Peter,
Klungland Arne,
Bjelland Svein
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601662
Subject(s) - biology , 5 methylcytosine , dna , microbiology and biotechnology , enzyme , genetics , dna methylation , biochemistry , gene , gene expression
N 1 ‐methyladenine (m 1 A) and N 3 ‐methylcytosine (m 3 C) are major toxic and mutagenic lesions induced by alkylation in single‐stranded DNA. In bacteria and mammals, m 1 A and m 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 1 A and m 3 C are repaired by the Af AlkA base excision repair glycosylase of Archaeoglobus fulgidus , suggesting a different repair mechanism for these lesions in the third domain of life. In addition, Af AlkA was found to effect a robust excision of 1, N 6 ‐ethenoadenine. We present a high‐resolution crystal structure of Af AlkA, which, together with the characterization of several site‐directed mutants, forms a molecular rationalization for the newly discovered base excision activity.