title: Structural basis for enzymatic excision of N1-methyladenine and N3-methylcytosine from DNA.
abstract: 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 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(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.
authors: The Norwegian Structural Biology Centre, University of Tromsø, Tromsø, Norway.
authors: Ingar
authors: I
authors: Leiros
authors: Marivi P
authors: MP
authors: Nabong
authors: Kristin
authors: K
authors: Grøsvik
authors: Jeanette
authors: J
authors: Ringvoll
authors: Gyri T
authors: GT
authors: Haugland
authors: Lene
authors: L
authors: Uldal
authors: Karen
authors: K
authors: Reite
authors: Inger K
authors: IK
authors: Olsbu
authors: Ingeborg
authors: I
authors: Knaevelsrud
authors: Elin
authors: E
authors: Moe
authors: Ole A
authors: OA
authors: Andersen
authors: Nils-Kåre
authors: NK
authors: Birkeland
authors: Peter
authors: P
authors: Ruoff
authors: Arne
authors: A
authors: Klungland
authors: Svein
authors: S
authors: Bjelland
mesh_terms: D000595:Amino Acid Sequence; D019611:Archaeoglobus fulgidus / Q000235:genetics*; D001483:Base Sequence; D018360:Crystallography, X-Ray; D004249:DNA Damage; D045647:DNA Glycosylases / Q000737:chemistry* / Q000235:genetics*; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D045647:DNA Glycosylases; C076131:DNA-3-methyladenine glycosidase II