title: Crystallographic studies on damaged DNAs. II. N(6)-methoxyadenine can present two alternate faces for Watson-Crick base-pairing, leading to pyrimidine transition mutagenesis.
abstract: In a previous paper, 2'-deoxy-N(6)-methoxyadenosine (mo(6)A) was shown to form a mismatch base-pair with 2'-deoxycytidine with a Watson-Crick-type geometry. To fully understand the structural basis of genetic mutations with damaged DNA, it is necessary to examine whether the methoxylated adenine residue still has the ability to form the regular Watson-Crick pairing with a thymine residue. Therefore, a DNA dodecamer with the sequence d(CGCGmo(6)AATTCGCG) has been synthesized and its crystal structure determined. The methoxylation has no significant effect on the overall DNA conformation, which is that of a standard B-form duplex. The methoxylated adenine moieties adopt the amino tautomer with an anti conformation around the C(6)-N(6) bond to the N(1) atom, and they form a Watson-Crick base-pair with thymine residues on the opposite strand, similar to an unmodified adenine residue. It is concluded that methoxylated adenine can present two alternate faces for base-pairing, thanks to the amino<-->imino tautomerism allowed by methoxylation. Based on this property, two gene transition routes are proposed.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuda, Midori-ku, Yokohama, 226-8501, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Chatake
authors.forename: T
authors.initials: T
authors.lastname: Hikima
authors.forename: A
authors.initials: A
authors.lastname: Ono
authors.forename: Y
authors.initials: Y
authors.lastname: Ueno
authors.forename: A
authors.initials: A
authors.lastname: Matsuda
authors.forename: A
authors.initials: A
authors.lastname: Takénaka
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D020029:Base Pairing; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D004583:Electrons; D006860:Hydrogen Bonding; D007536:Isomerism; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics*; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013941:Thymine / Q000378:metabolism*
chemical_list: C073276:N(6)-methoxyadenine; D004247:DNA; D000225:Adenine; D013941:Thymine