Ribonucleoside-Diphosphate Reductase Subunit M2 (RRM2) belongs to the ribonucleoside diphosphate reductase small chain family. The reductase of RRM2 catalyzes the formation of deoxyribonucleotides from ribonucleotides. Synthesis of the encoded protein (M2) is regulated in a cell-cycle dependent fashion. RRM2 supplies the precursors essential for DNA synthesis. RRM2 catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Phosphorylation on Ser-20 relieves the inhibitory effect on Wnt signaling.

RRM1 is a subunit of ribonucleoside-diphosphate reductase which is constituted by two subunits. Ribonucleoside-diphosphate reductase is an enzyme essential for the production of deoxyribonucleotides prior to DNA synthesis in S phase of dividing cells. RRM1 is one of several genes located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. RRM1 may play a role in malignancies and disease that involve this region.

Ribonucleoside reductase subunit M2B, also known as RRM2B or p53R2, is an enzyme belonging to the iron-dependent ribonucleotide reductase (RNR) enzyme family which is essential for DNA synthesis. Ribonucleotide reductase (RNR) is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides and plays a critical role in regulating the total rate of DNA synthesis so that DNA to cell mass is maintained at a constant ratio during cell division and DNA repair. RRM2B is a phosphorylated protein. It is hypothesized that RRM2B activity can be regulated at the posttranslational level in response to DNA damage. RRM2B has previously been shown to be essential for the maintenance of mtDNA copy number and its candidacy for tumor suppression has been evaluated in several mutational analyses of different cancer types. However, the contribution of RRM2B to the DNA damage response has been questioned because its transcriptional induction upon DNA damage is not rapid enough for prompt DNA repair. Instead, ATM-mediated phosphorylation has been suggested to regulate the DNA repair activity of RRM2B posttranslationally. Besides, a defect in RRM2B can induce a mild muscle disease of adult onset through disturbance of mitochondrial homeostasis but that this defect does not appear to be oncogenic.

Thioredoxin-2, also known as TXN2, MTRX and TRX2, is a member of the thioredoxin family. Tryparedoxins (TXN) are thioredoxin-related proteins which, as trypanothione:peroxiredoxin oxidoreductases, constitute the trypanothione-dependent antioxidant defense and may also serve as substrates for ribonucleotide reductase in trypanosomatids. Thioredoxin-2 / TXN2 contains one thioredoxin domain. It is widely expressed in adult (at protein level) and fetal tissues. Human Thioredoxin-2 / TXN2 is a small redox protein important in cellular antioxidant defenses, as well as in the regulation of apoptosis. Thioredoxin-2 / TXN2 has an anti-apoptotic function and plays an important role in the regulation of mitochondrial membrane potential. Thioredoxin-2 / TXN2 could be involved in the resistance to anti-tumor agents. It possesses a dithiol-reducing activity. Thioredoxin-2 / TXN2 plays an important role in protecting the mitochondria against oxidative stress and in sensitizing the cells to ROS-induced apoptosis. Mammalian Thioredoxin-2 / TXN2 is a mitochondrial isoform of highly evolutionary conserved thioredoxins. Thioredoxins are small ubiquitous protein-disulfide oxidoreductases implicated in a large variety of biological functions.

Glutaredoxin-1, also known as GRX1 and GLRX, belongs to theglutaredoxin family. Glutaredoxinsare smallredoxenzymes that useglutathioneas a cofactor. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. Glutaredoxin-1 functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Glutaredoxin-1 exists in either a reduced or an oxidized form. Glutaredoxins function as electron carriers in the glutathione-dependent synthesis ofdeoxyribonucleotidesby the enzymeribonucleotide reductase.