The last step is the reverse of the first step and involves a hydrogen transfer from Cys439 to C-3’, regenerating the initial radical and resulting in the final product 6. Theoretical models of some steps of these mechanisms using the full model of the R1 protein can be found at the studies performed by Cerqueira et al.. Regulation Class I RNR comprises RNR1 and RNR2 subunits, which can associate to form a heterodimeric tetramer. RNR1 contains both allosteric sites, mediating regulation of substrate specificity and activity. Depending on the allosteric configuration, one of the four ribonucleotides binds to the active site. Regulation of RNR is designed to maintain balanced quantities of dNTPs. Binding of effector molecules either increases or decreases RNR activity. When ATP binds to the allosteric activity site, it activates RNR. In contrast, when dATP binds to this site, it deactivates RNR. In addition to controlling activity, the allosteric mechanism also regulates the substrate specificity and ensures the enzyme produces an equal amount of each dNTP for DNA synthesis. In all classes, binding of ATP or dATP to the allosteric site induces reduction of cytidine 5’-diphosphate (CDP) and uridine 5’-diphosphate (UDP); 2’-deoxyguanosine 5’-triphosphate (dGTP) induces reduction of adenosine 5’-diphosphate (ADP); and 2’-deoxythymidine 5’-triphosphate (dTTP) induces reduction of guanosine 5’-diphosphate (GDP) (Figure 1). Class IB reductases are not inhibited by dATP because they lack approximately 50 N-terminal amino acids required for the allosteric activity site. Additionally, it is important that the activity of ribonucleotide reductase be under transcriptional and post-transcriptional control because the synthesis of damage-free DNA relies on a balanced pool of deoxyribonucleotides. Eukaryotic cells with class IA reductases have a mechanism of negative control to turn off synthesis of dNTPs as they accumulate. This mechanism protects the cell from toxic and mutagenic effects that can arise from the overproduction of dNTPs because changes in balanced dNTP pools lead to DNA damage and cell death. Although, the overproduction of dNTPs or an unbalanced supply of them can lead to misincorporation of nucleotides into DNA, the supply of dNTPs supply can allow for DNA repair. p53R2 is a small subunit of ribonucleotide reductase that can induce such repair. Changes within this p53 induced R2 homolog can cause depletion in mitochondrial DNA and consequently p53R2 serves a major factor in dNTP supply. RNR may use the morpheein model of allosteric regulation. RNR1 and RNR2 inhibitors Generally Class I RNR inhibitors