THE ROLE OF METALS IN THE HYDROLYTIC CLEAVAGE OF DNA AND RNA

The nucleic acids RNA and DNA consist of nucleoside building blocks jo ined by phosphodiester linkages. Phosphodiesters are generally inert t o hydrolytic cleavage under physiological conditions because their neg ative charge disfavors nucleophilic attack. However, the hydrolytic sc ission of phosphodiester linkages is an important and common biologica l process, and can occur rapidly in the presence of appropriate cataly sts such as ribozymes and nuclease enzymes. Metals play an important r ole in this process. Several possible modes of action can be invoked f or metal-promoted phosphate ester hydrolysis, including Lewis acid cat alysis, Bronsted base catalysis by metal-bound hydroxides, nucleophili c catalysis by metal-bound hydroxides, Bronsted acid catalysis by meta l-bound water, and electrostatic stabilization of transition states by positively charged metal ions. Here we critically discuss the roles o f metals in the hydrolytic cleavage of nucleic acids and related model substrates.