Ribonucleotide reductase large subunit (RRM1); Ribonucleotide reductase small subunit (RRM2) (RRM1 (for large subunit), RRM2 (for small subunit))

Ribonucleotide reductase is the enzyme responsible for converting ribonucleotides into deoxyribonucleotides, thereby providing the essential precursors for DNA replication and repair. The holoenzyme consists of two subunits: the large catalytic subunit (RRM1) and the small regulatory subunit (RRM2). RRM1 catalyzes the reduction reaction, while RRM2 generates and stabilizes a tyrosyl radical necessary for catalysis. The activity and specificity of ribonucleotide reductase rely on complex allosteric regulation, cell cycle-dependent expression, and post-translational modifications including acetylation and phosphorylation. Dysregulation or aberrant expression of RRM1/RRM2 is associated with tumor progression, therapy resistance, and adverse prognosis, making them prominent targets for cancer therapy. Drugs such as gemcitabine and hydroxyurea inhibit their activity, aiming to limit DNA synthesis in rapidly dividing cancer cells.

Other names

ribonucleoside-diphosphate reductase large subunitRR1RNR1ribonucleoside-diphosphate reductase small subunitRR2RNR2

Inhibition of deoxyribonucleotide synthesis (stopping DNA synthesis/repair and cell proliferation); Induction of DNA replication fork stalling