Ribonucleotide reductases: amazing and confusing.

Abstract

Ribonucleotide reductases play a central role in DNA biosynthesis catalyzing the conversion of NDPs (NTPs) to dNDPs (dNTPs) (l-5) concomitant with oxidation of thiols within their active sites (Equation 1) (6). A single active site can accommodate reduction of both purines and pyrimidines. With the exception of the viral reductases (7)’ the substrate specificity of the proteins is governed by the choice of appropriate allosteric effecters (5,8). The importance of maintaining controlled dNTP pool sizes to the fidelity of DNA replication mandates interactive multifaceted regulatory mechanisms of ribonucleotide reductases. These include transcriptional (9) and translational control (10) and perhaps enzymatic modulation of the production and destruction of active cofactor (11-13). The recent cloning, sequencing, and expression of reductases from a variety of sources (14-22) should allow a detailed investigation of these regulatory mechanisms in the next few years. The central role of ribonucleotide reductases in DNA biosynthesis also has made them a desirable target for the design of antitumor agents (5, 23, 24) and more recently antiviral agents (25-30).