Crystallographic studies on damaged DNAs. II. N-6-methoxyadenine can present two alternate faces for Watson-Crick base-pairing, leading to pyrimidinetransition mutagenesis

In a previous paper, 2'-deoxy-N-6-methoxyadenosine (mo(6)A) was shown to fo rm a mismatch base-pair with 2'-deoxycytidine with a Watson-Crick-type geom etry. To fully understand the structural basis of genetic mutations with da maged DNA, it is necessary to examine whether the methoxylated adenine resi due still has the ability to form the regular Watson-Crick pairing with a t hymine residue. Therefore, a DNA dodecamer with the sequence d(CGCGmo(6)AAT TCGCG) has been synthesized and its crystal structure determined. The metho xylation has no significant effect on the overall DNA conformation, which i s 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 th e 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 concl uded that methoxylated adenine can present two alternate faces for base-pai ring, thanks to the amino <----> imino tautomerism allowed by methoxylation . Based on this property, two gene transition routes are proposed. (C) 1999 Academic Press.