Cellular regulation of ribonucleotide reductase in eukaryotes.
Synthesis of deoxynucleoside triphosphates (dNTPs) is essential for both DNA replication and repair and a key step in this process is catalyzed by ribonucleotide reductases (RNRs), which reduce ribonucleotides (rNDPs) to their deoxy forms. Tight regulation of RNR is crucial for maintaining the correct levels of all four dNTPs, which is important for minimizing the mutation rate and avoiding genome instability. Although allosteric control of RNR was the first discovered mechanism involved in regulation of the enzyme, other controls have emerged in recent years. These include regulation of expression of RNR genes, proteolysis of RNR subunits, control of the cellular localization of the small RNR subunit, and regulation of RNR activity by small protein inhibitors. This review will focus on these additional mechanisms of control responsible for providing a balanced supply of dNTPs.
Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom. Electronic address: estrellaguarino@gmail.com.
Estrella
E
Guarino
Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom. Electronic address: iscorbacho@gmail.com.
Israel
I
Salguero
Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom. Electronic address: stephen.kearsey@zoo.ox.ac.uk.
Stephen E
SE
Kearsey
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002453:Cell Cycle; D004260:DNA Repair; D004261:DNA Replication; D003854:Deoxyribonucleotides / Q000096:biosynthesis; D025461:Feedback, Physiological; D042822:Genomic Instability; D006801:Humans; D012264:Ribonucleotide Reductases / Q000502:physiology*
D003854:Deoxyribonucleotides; D012264:Ribonucleotide Reductases
DNA repair; DNA synthesis; Deoxyribonucleotide pools; Genome stability