Ribonucleotide reductase catalytic subunit M1 (RRM1) (RRM1)

Ribonucleotide reductase catalytic subunit M1 (RRM1) is the large catalytic subunit of the ribonucleotide reductase (RR) enzyme complex, which is responsible for the de novo synthesis of deoxyribonucleotides (dNTPs) from ribonucleotides [1, 7]. This process is the rate-limiting step in DNA replication and repair, making RRM1 a vital regulator of the cell cycle and genomic stability [1, 6, 10]. In clinical oncology, RRM1 is a major therapeutic target for several antimetabolite drugs, including gemcitabine and clofarabine, which inhibit the enzyme to deplete the nucleotide pools necessary for cancer cell proliferation [5, 8, 13]. High expression of RRM1 is frequently associated with resistance to these chemotherapeutic agents and poor prognosis in various malignancies, such as non-small cell lung cancer and pancreatic cancer [4, 5, 10]. Consequently, RRM1 levels serve as a significant biomarker for predicting treatment response and guiding personalized therapy [2, 4, 7]. Beyond its catalytic role, RRM1 has been implicated in regulating cell migration and tumor progression, highlighting its multifaceted importance in cancer biology [4, 8].

Other names

Ribonucleoside-diphosphate reductase large subunitRibonucleoside-diphosphate reductase subunit M1Ribonucleotide reductase M1 polypeptideRibonucleotide reductase, R1 subunitR1RR1

Inhibition of the enzyme prevents the conversion of ribonucleotides to deoxyribonucleotides, thereby depleting the cellular pools of deoxyribonucleotide triphosphates (dNTPs) and stalling DNA synthesis and repair, which leads to cell cycle arrest and apoptosis [1, 5, 6, 8].