Ribonucleotide reductase small subunit (RNR small subunit (also referred to as R2 in the context of human enzymes))

Ribonucleotide reductase small subunit, typically known as the **R2 subunit** (encoded by **RRM2** or **RRM2B** in humans), is a critical component of the class I ribonucleotide reductase enzyme. The RNR complex catalyzes the reduction of ribonucleotides to deoxyribonucleotides—the rate-limiting step in DNA synthesis essential for cell proliferation and repair[1][2][3]. The small subunit harbors a diferric-tyrosyl radical cofactor in humans, which is required for long-range electron transfer during catalysis. RNR activity and specifically the expression level of the R2 subunit are tightly regulated, as overexpression is linked to cancer progression and poor prognosis[3]. Several chemotherapeutic drugs target RNR, and inhibition of the R2 subunit leads to depletion of deoxyribonucleotide pools, DNA synthesis arrest, and cell death—an approach particularly cytotoxic to rapidly dividing cells such as cancer cells[2][3][4].

Other names

RNR small subunitR2 subunitRRM2 (human gene symbol)RRM2B (alternative human gene, p53-inducible variant)Ribonucleoside-diphosphate reductase subunit beta

Inhibition of radical formation/maintenance (e.g., hydroxyurea scavenges the tyrosyl radical) Direct binding and inhibition of subunit interaction (TAS1553 disrupts R1-R2 interaction) Antimetabolites (nucleoside analogs act as substrate mimics/inhibitors)