Crystallographic studies on damaged DNAs. I. An N-6-methoxyadenine residueforms a Watson-Crick pair with a cytosine residue in a B-DNA duplex

Oxyamines such as hydroxylamine and methoxylamine disturb DNA replication a nd act as potent mutagens, causing nucleotide transition from one purine to another or one pyrimidine to another. In order to investigate mismatch bas e-pairing in DNA damaged with oxyamines, a dodecamer with the sequence d(CG CGmo(6)AATCCGCG), where mo(6) A is 2'-deoxy-N-6-methoxyadenosine, was synth esized 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 residu e forms a basepair with a 2'-deoxycytidine residue through hydrogen bonds s imilar 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, misinc orporation of 2'-deoxycytidine instead of thymidine, or 2'-deoxy-adenosine instead of 2'-deoxyguanosine, can occur in DNA replication. (C) 1999 Academ ic Press.