Structural polymorphism of homopurine DNA sequences. d(GGA)n and d(GGGA)n repeats form intramolecular hairpins stabilized by different base-pairing interactions.

Abstract

DNA sequences containing homopurine d(G1-3A)n tracts are known to be capable of adopting non-B-DNA conformations. The structural polymorphism of these sequences is a direct consequence of the structural properties of the homopurine d(G1-3A)n tracts. Depending on the conditions, d(GA)n DNA sequences can form antiparallel-and parallel-stranded homoduplexes, multistranded complexes, and ordered single-stranded conformations. On the other hand, much less is known about the structural properties of d(GGA)n and d(GGGA)n sequences. In this paper, we show that d(GGA)n and d(GGGA)n repeats form antiparallel-stranded, intramolecular hairpins. Under physiological salt and pH conditions, the thermal stability of these hairpin forms is high, showing, at 50 mM NaCl, melting temperatures in the range of 40-50 degrees C. The base-pairing interactions involved in the formation of the d(GGA)n and d(GGGA)n hairpins are different. G.A pairs importantly contribute to the stability of the d(GGA)n hairpins. On the other hand, the d(GGGA)n hairpins are stabilized by the formation of G.G and A.A, but not G.A pairs. Homopurine d(G1-3A)n tracts are frequently found at genomic locations performing specialized chromosomal functions (i.e. telomeres, centromeres, and recombination "hot-spots"). The molecular interactions described here are relevant for the understanding of the peculiar structural and biological properties of DNA sequences containing homopurine tracts.