Nearest-Neighbor Effects in the Structure and Function of Nucleic Acids

Abstract

This article examines the hypothesis, called the RY model, that these extended stacks occur in the special arrangements of purines (R) and pyrimidines (Y) along the chains. The RY model comes from the measurements of the nuclear magnetic resonance (nmr) chemical shifts in oligoribonucleotide and finds some support in X-ray diffraction studies. The model will evolve into a more comprehensive picture when the nearest-neighbor effects are characterized more thoroughly by further experiments. The purpose is to stimulate the molecular biologists to think beyond sequence, to consider the arrangement of nearest neighbors. It is largely these neighbor interactions that determine the local three dimensional shape imparted by the sequence. The A-form may represent the conformation of DNA in its actively expressed form. B-DNA may be a form useful for storage rather than expression of genetic content, although enzymes may also use its special plasticity in “induced-fit’’ interactions. The left-handed Z-form exists only in specific sequences and is in a delicate balance with the right-handed B-form, easily shifted by solution conditions. Z-DNA may be especially important in regulating torsional stress in supercoiled DNA.