RNR1

Rnr1 is the gene encoding the large subunit of ribonucleotide reductase (RNR) in eukaryotes, with a well-studied example in the budding yeast Saccharomyces cerevisiae. The protein produced by Rnr1 acts as the catalytic subunit of class I ribonucleotide reductase and, together with a smaller subunit, forms the active holoenzyme that reduces ribonucleoside diphosphates to deoxyribonucleoside diphosphates, the precursors needed for DNA synthesis and repair.

In Saccharomyces cerevisiae, Rnr1 is essential for viability. The enzyme is most active during S phase and its activity is regulated by intracellular dNTP pools, as well as by cellular cues such as DNA damage and replication stress. The yeast small subunit that partners with Rnr1 comprises Rnr2 and Rnr4, which together provide the necessary radical-generating component to support catalysis.

Regulation of Rnr1 occurs at multiple levels. Allosteric effectors, including ATP and dATP, modulate enzyme activity and substrate specificity to balance dNTP production. Transcription of RNR1 can be upregulated in response to DNA damage or replication stress via the cell’s damage response pathways. Inhibitors like hydroxyurea suppress ribonucleotide reductase activity, leading to depletion of dNTP pools and inhibition of DNA replication.

Rnr1 has homologs across organisms; in bacteria the large subunit is typically called NrdA, and in humans the functional analog is the R1 subunit of ribonucleotide reductase. These enzymes are central to maintaining balanced dNTP pools necessary for faithful DNA synthesis.