Document Type

Article

Publication Date

2003

Abstract

Structures of the DNA sequences d(CCGGCGCCGG) and d(CCAGTACbr5UGG) are presented here as four-way Holliday junctions in their compact stacked-X forms, with antiparallel alignment of the DNA strands. Thus, the ACC-trinucleotide motif, previously identified as important for stabilizing the junction, is now extended to PuCPy, where Pu is either an adenine or guanine, and Py is either a cytosine, 5-methylcytosine, or 5-bromouracil but not thymine nucleotide. We see that both sequence and base substituents affect the geometry of the junction in terms of the interduplex angle as well as the previously defined conformational variables, Jroll (the rotation of the stacked duplexes about their respective helical axis) and Jslide (the translational displacement of the stacked duplexes along their respective helical axis). The structures of the GCC and parent ACC containing junctions fall into a distinct conformational class that is relatively undistorted in terms of Jslide and Jroll, with interduplex angles of 40-43°. The substituted ACbr5U structure, however, is more akin to that of the distorted methylated ACm5C containing junction, with Jslide (g2.3 Å) and a similar Jroll (164°) opening the major groove-side of the junction, but shows a reduced interduplex angle. In contrast, the analogous d(CCAGTACTGG) sequence has to date been crystallized only as resolved B-DNA duplexes. This suggests that there is an electronic effect of substituents at the pyrimidine Py position on the stability of four-stranded junctions. The single-crystal structures presented here, therefore, show how sequence affects the detailed geometry, and subsequently, the associated stability and conformational dynamics of the Holliday junction.

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