Ribonucleotide reductase large subunit (RRM1) (RRM1)

Ribonucleotide reductase large subunit (RRM1) is the catalytic component of the ribonucleotide reductase (RR) enzyme complex, which is essential for de novo synthesis of deoxyribonucleotides (dNTPs) [UniProt: P23921]. By catalyzing the reduction of ribonucleoside diphosphates into their corresponding deoxyribonucleoside forms, RRM1 provides the necessary building blocks for DNA replication and repair [NCBI: 6240]. This enzyme is highly regulated throughout the cell cycle, with peak activity during the S-phase to support genomic duplication [PubMed: 17634284]. In oncology, RRM1 is a critical therapeutic target because its overexpression is frequently associated with tumor progression and resistance to nucleoside analog drugs [PubMed: 21533170]. Several chemotherapeutic agents, such as gemcitabine and clofarabine, act as antimetabolites that inhibit RRM1 activity or compete for its active site, leading to dNTP pool depletion and subsequent apoptosis [DrugBank: DB00441]. Furthermore, RRM1 expression levels serve as a significant biomarker for predicting patient response to gemcitabine-based chemotherapy regimens, particularly in non-small cell lung cancer [PubMed: 17634284]. Therapeutic strategies targeting RRM1 often involve combination therapies to overcome resistance mechanisms and enhance the efficacy of DNA-damaging agents [PubMed: 21533170].

Other names

R1 subunitRibonucleoside-diphosphate reductase large subunitRibonucleoside-diphosphate reductase subunit M1RRM1

Inhibition of the catalytic subunit of ribonucleotide reductase, leading to the depletion of deoxyribonucleotide triphosphate (dNTP) pools, which results in the termination of DNA synthesis and induction of apoptosis [DrugBank: DB00441, PubMed: 21533170].