Nucleases : diversity of structure, function and mechanism

Nucleases cleave the phosphodiester bonds of nucleic acids and may be endo orexo, DNase or RNase, topoisomerases, recombinases, ribozymes, or RNA splicing enzymes. Inthis review, I survey nuclease activities with known structures and catalytic machinery andclassify them by reaction mechanism and metal-ion dependence and by their biologicalfunction ranging from DNA replication, recombination, repair, RNA maturation, processing,interference, to defense, nutrient regeneration or cell death. Several general principles emergefrom this analysis. There is little correlation between catalytic mechanism and biologicalfunction. A single catalytic mechanism can be adapted in a variety of reactions and biologicalpathways. Conversely, a single biological process can often be accomplished by multipletertiary and quaternary folds and by more than one catalytic mechanism. Two-metal-ion-dependent nucleases comprise the largest number of different tertiary folds and mediate themost diverse set of biological functions. Metal-ion-dependent cleavage is exclusively associatedwith exonucleases producing mononucleotides and endonucleases that cleave double- orsingle-stranded substrates in helical and base-stacked conformations. All metal-ion-independentRNases generate 2k,3 k -cyclic phosphate products, and all metal-ion-independent DNases formphospho-protein intermediates. I also find several previously unnoted relationships betweendifferent nucleases and shared catalytic configurations