DNA can adopt many other structures beyond the canonical B-form double helix.
These alternative DNA structures have become increasingly significant as new
biological roles are found for them. Additionally, there has been a growing
interest in using non-canonical base pairs to provide structural diversity for
designing DNA architectures for nanotechnology applications. We recently
described the crystal structure of d(ACTCGGATGAT), which forms a tetraplex
through parallel-stranded homo-base pairs and nucleobase intercalation. The
homoduplex region contains a d(YGA⋅YGA) motif observed in crystal and solution
structures. Here, we examine the structural implications of the homopyrimidine
base pair within this motif. We determined crystal structures of two variants
that differ from the original structure in the homopyrimidine base pairs and
number of d(YGA) motifs. Our results show that the intercalation-locked
tetraplex motif is predictable in these different sequence contexts and that
substituting C⋅C base pairs for T⋅T base pairs introduces asymmetry to the
homoduplex. These results have important implications for utilizing d(YGA)
motifs in DNA crystal design and could provide a basis for understanding how
local structures could be associated with repeat expansions.
