Ribonucleoside-diphosphate reductase subunit M2 (RRM2) (RRM2)

Ribonucleoside-diphosphate reductase subunit M2 (RRM2) is the small, regulatory subunit of the class I ribonucleotide reductase (RNR) enzyme complex, which catalyzes the rate-limiting step in the de novo synthesis of deoxyribonucleotides (dNTPs) [1, 4]. By reducing ribonucleoside diphosphates into their corresponding deoxy forms, RRM2 provides the essential building blocks required for DNA replication and repair [1, 2]. Its expression is strictly regulated according to the cell cycle, peaking during the S-phase to support rapid DNA synthesis [1, 6]. In many malignancies, RRM2 is frequently overexpressed or amplified, contributing to uncontrolled cell proliferation, genomic instability, and resistance to various chemotherapeutic agents [1, 10, 15]. As a result, RRM2 is a significant therapeutic target in oncology, with inhibitors like hydroxyurea and triapine acting by quenching the essential tyrosyl radical or chelating the iron cofactor within the subunit [1, 11]. Beyond its primary enzymatic function, RRM2 also plays roles in suppressing ferroptosis and modulating immune infiltration, making it a critical factor in tumor progression and a valuable prognostic biomarker [1, 15, 16].

Other names

Ribonucleotide reductase regulatory subunit M2Ribonucleotide reductase small subunitRibonucleotide reductase small chainR2RR2RR2MC2orf48

Inhibition of the ribonucleotide reductase enzyme complex by targeting the M2 subunit, leading to the depletion of deoxyribonucleotide (dNTP) pools, which halts DNA synthesis and repair, induces cell cycle arrest, and triggers apoptosis [1, 11].