Jk. Bashkin et La. Jenkins, THE ROLE OF METALS IN THE HYDROLYTIC CLEAVAGE OF DNA AND RNA, Comments on modern chemistry. Part A, Comments on inorganic chemistry, 16(1-2), 1994, pp. 77-93
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.