Nucleic Acid–Metal Ion Interactions

Abstract Nucleic acids (DNA and RNA) are actually salts (or complexes) of metal ions from a chemical point of view. It is impossible to separate the behavior of DNA and RNA from their interactions with metal ions. Metal ions are usually required to promote and stabilize functionally active or native conformations of nucleic acids, as well as to mediate nucleic acid‐protein interactions. However, certain metal ions can also cause structural transformation of nucleic acids, and induce their chemical modification and cleavage. Metal‐nucleic acid interactions are involved in nucleotide biochemistry; genetic information storage and transfer, and control of gene expression, as well as in mutagenesis and carcinogenesis. However, in most cases, it is not currently clear whether the observed effects actually result from direct metal ion‐nucleic acid interaction, since other species, such as specific proteins, may be mediators between the metal ion and the nucleic acid in these processes in vivo . Interest in metal‐nucleic acid interactions is also enhanced by studies of the mechanisms of antitumor activity of certain platinum metal compounds, finding metal ions in crystal structure of natural RNA molecules, studies of the mechanism of RNA catalysis and possible involvement of metal ions in origin of life, as well as by the use of metal ions as structural probes of nucleic acids and as biotechnology tools. This article does not attempt to be comprehensive, but rather presents selected examples to illustrate key facets of metal ion‐nucleic acid interaction. The focus is on the chemical and structural properties of both nucleic acids and metal ions relevant to their interactions. Nucleic acid‐metal interactions can be either nonspecific or dependent on the chemical nature, sequence, and structure of nucleic acids. However, the specificity of these interactions is dependent on structural and chemical properties of both the nucleic acids and the metal ions. Both nucleic acids and metal ions exhibit considerable complexity in their interactions, and such interactions could affect the chemical and biochemical properties of both species.