Unresolved issues in the study of mammalian ribonucleotide reductase

Although research on mammalian ribonucleotide reductase and its role in cell replication has been intensified in recent years, there remain several areas in which there is not uniform agreement with respect to several of its important properties. The major issues include: 1) whether there is one enzyme which catalyzes the reduction of all four substrates or several enzymes for the four substrates; 2) whether the two subunits are coordinately regulated as the cells pass from G1 to S during the cell cycle; if not which subunit represents the limiting component and what are the respective half-lives of the individual subunits; 3) whether the allosteric regulation which has been demonstrated in the test tube is the actual mechanism in the intact cells; and 4) is mammalian ribonucleotide reductase part of an enzyme complex which channels ribonucleoside diphosphates into DNA. The data which have appeared in the literature are discussed in the context of these unresolved questions.