The extended and eccentric E-DNA structure induced by cytosine methylationor bromination

Cytosine methylation or bromination of the DNA sequence d(GGCGCC)(2) is sho wn here to induce a novel extended and eccentric double helix, which we cal l E-DNA. Like B-DEJA, E-DNA has a long helical rise and bases perpendicular to the helix axis. However, the 3'-endo sugar conformation gives the chara cteristic deep major groove and shallow minor groove of A-DNA. Also, if all owed to crystallize for a period of time longer than that yielding E-DNA, t he methylated sequence forms standard A-DNA, suggesting that E-DNA is a kin etically trapped intermediate in the transition to A-DNA. Thus, the structu res presented here chart a crystallographic pathway from B-DNA to A-DNA thr ough the E-DNA intermediate in a single sequence. The E-DNA surface is high ly accessible to solvent, with waters in the major groove sitting on expose d faces of the stacked nucleotides. We suggest that the geometry of the wat ers and the stacked base pairs would promote the spontaneous deamination of fi-methylcytosine in the transition mutation of dm(5)C-dG to dT-dA base pa irs.