Quadruple intercalated G-6 stack: a possible motif in the fold-back structure of the Drosophila centromeric dodeca-satellite?

The purine-rich strand d(GTACGGGACCGA)n of the Drosophila centromeric dodeca-satellite sequence is highly conserved and was found to form stable fold-back structures in which the homopurine 5′-GGGA-3′ sequence was determined to play a crucial role. Here, we report the stable formation of the d(GGGA)2 motif in the stem of a DNA hairpin closed by a single-residue d(ACC) loop. Similar to the zipper-like d(GGA)2 motif observed in the human centromeric (TGGAA)n sequence, the central four guanosine bases in the d(GGGA)2 motif do not pair, but interdigitate to form an elongated zipper-like quadruple-intercalated G-6 stack bracketed by sheared G·A base-pairs. Comparison between the current d(GGGA)2 structure and the published crystal d(GAAA)2 structure implies that the alignment of the unpaired purine bases plays an important role in determining the minor groove width of the purine-rich d(GPuPuA)2 motif. Similarity between the zipper-like motifs possibly present in the Drosophila centromeric dodeca-satellite sequence and in the human centromeric (TGGAA)n sequence led us to propose that these special zipper-like motifs may constitute common cores in organizing eukaryotic centromeres.