Ribonucleotide Reductases: Influence of Environment on Synthesis and Activity

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Abstract
Ribonucleotide reductases (RNRs) are enzymes that provide deoxyribonucleotides (dNTPs), the building blocks required for de novo DNA synthesis and repair. They are found in all organisms from prokaryotes to eukaryotes. Interestingly, in the microbial world, several organisms possess the genes encoding two, or even three different RNRs that present different structures and allosteric regulation. The finding of an increasing number of bacterial species that possess more than one RNR might suggest particular functions for these enzymes in different growth conditions. Recent support for this proposal comes from studies indicating that expression and activity of the different RNRs depends on the environment. The oxygen content as well as the redox and oxidative stresses regulate RNR activity and synthesis in various organisms. This regulation has a direct consequence on dNTP pools. An excess of dNTP pools that leads to misincorporation of dNTPs results in genetic abnormalities in eukaryotes as in prokaryotes. In contrast, increased dNTP concentrations help cells to survive under conditions where DNA has been damaged. Hence the use of different RNRs in response to various environmental conditions allows the cell to regulate the amount precisely of dNTP in both a positive and negative manner so that enough, yet not excessive, dNTPs are synthesized.