Divalent cations stabilize unstacked conformations of DNA and RNA by interacting with base Pi systems

Nucleic acid structure, stability, and reactivity are governed substantiall y by cations. We propose that magnesium and other biological inorganic ions unstack bases of DNA and RNA. This unstacking function of cations opposes their previously accepted role in stabilizing DNA and RNA duplexes and high er assemblies. We show that cations interact favorably with pi-systems of n ucleic acid bases. These cation-m interactions require access of cations or their first hydration shells to faces of nucleic acid bases. We observe th at hydrated magnesium ions located in the major groove of B-DNA pull cytosi ne bases partially out from the helical stack, exposing pi-systems to posit ive charge. A series of critical cation-pi interactions contribute to the s tability of the anticodon arm of yeast-tRNA(phe), and to the magnesium core of the Tetrahymena group I intron P4-P6 domain. The structural consequence s of divalent cation-pi interactions are clearly distinct from, and some ca ses in opposition to, cation-electron lone pair interactions. These observa tions of cation-pi interactions suggest a number of new mechanistic roles f or cations in DNA bending, DNA-protein recognition, base-flipping, RNA fold ing, and catalysis.