Sequence-dependent variations in the backbone geometry of a synthetic DNA fibre

Abstract

There are many examples of proteins which interact with specific DNA sequences (see references cited in refs 1 and 2). It is not clear whether specificity is derived from proteins sensing directly the base sequence of the DNA or is a result of unique secondary or tertiary structural features induced by certain DNA sequences. Recent studies have indicated the occurrence of several types of symmetries and sequence irregularities in DNA regions which interact with regulatory proteins, but they do not provide information on three-dimensional structure³. The Watson–Crick base-paired double helix can be observed in different conformations^4–6, depending on humidity and salt concentration. Within the limited resolution of X-ray fibre diffraction at high relative humidity and in the appropriate salt conditions, studies indicate that natural DNA as well as synthetic repeating polynucleotide duplexes adopt essentially the same average secondary structure, namely the B conformation⁷. This implies that all residues adopt a single backbone conformation. Recently, however, a high-resolution proton NMR study⁸ has demonstrated that a change from a regular conformation may occur at the junction region of block copolymers. ³¹P NMR studies strongly suggest that alternating polynucleotides can have alternating backbone conformations in solution^9,10. Klug et al.¹¹ have proposed an alternating structure for poly(dAdT)·poly(dAdT), based on a single crystal X-ray diffraction study of the tetranucleotide, dA-dT-dA-dT (ref. 12). We report here structural ³¹P NMR studies which show the existence of such variation in the fibre form of a synthetic DNA, poly(dAdT)·poly(dAdT). This confirms our earlier conclusion¹³ that natural DNA has a non-uniform backbone conformation.