title: Crystallographic studies on damaged DNAs. I. An N(6)-methoxyadenine residue forms a Watson-Crick pair with a cytosine residue in a B-DNA duplex.
abstract: Oxyamines such as hydroxylamine and methoxylamine disturb DNA replication and act as potent mutagens, causing nucleotide transition from one purine to another or one pyrimidine to another. In order to investigate mismatch base-pairing in DNA damaged with oxyamines, a dodecamer with the sequence d(CGCGmo(6)AATCCGCG), where mo(6) A is 2'-deoxy-N(6)-methoxyadenosine, was synthesized and its crystal structure determined. No significant conformational changes are found between the present dodecamer and the original undamaged B-form dodecamer. Electron density maps clearly show that the mo(6)A residue forms a base-pair with a 2'-deoxycytidine residue through hydrogen bonds similar to a Watson-Crick G.C base-pair. For these hydrogen bonds to be made, N(6)-methoxyadenine must chemically take the imino form. The methoxylation thus enables the adenine base to mimic a guanine base. As a result, misincorporation of 2'-deoxycytidine instead of thymidine, or 2'-deoxyadenosine instead of 2'-deoxyguanosine, can occur in DNA replication.
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: 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; D020137:Base Pair Mismatch; D020029:Base Pairing / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000378:metabolism*; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004249:DNA Damage; D004583:Electrons; D006860:Hydrogen Bonding; D007536:Isomerism; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation
chemical_list: C073276:N(6)-methoxyadenine; D003596:Cytosine; D004247:DNA; D008274:Magnesium; D000225:Adenine