Ribonucleotide reductase regulatory subunit M2B (RRM2B) (RRM2B)

Ribonucleotide reductase regulatory subunit M2B (RRM2B), also known as p53R2, is an essential enzyme subunit responsible for supplying deoxynucleotides (dNTPs) required for DNA repair and mitochondrial DNA (mtDNA) synthesis. Unlike the related RRM2 subunit, which is strictly expressed during the S-phase for bulk genomic DNA replication, RRM2B is induced by the p53 tumor suppressor protein in response to DNA damage and is expressed throughout the cell cycle, including in quiescent cells. This protein plays a critical role in maintaining genomic stability and protecting against mitochondrial depletion. [Source: UniProt P55944; PubMed: 10821268]. In oncology, RRM2B is often overexpressed in various solid tumors and is associated with poor prognosis and resistance to conventional chemotherapy and radiation. Therapeutic strategies focus on inhibiting the ribonucleotide reductase complex to deplete dNTP pools, thereby sensitizing cancer cells to DNA-damaging agents. However, targeting RRM2B also presents challenges, as germline mutations in the RRM2B gene are linked to severe mitochondrial DNA depletion syndromes, highlighting its vital role in non-dividing tissues like muscle and brain. [Source: PubMed: 28246114; OMIM: 604712].

Other names

p53R2p53-inducible ribonucleotide reductase small subunit 2-like proteinRibonucleoside-diphosphate reductase subunit M2BMTDPS8AMTDPS8B

Ribonucleotide reductase inhibition; quenching of the tyrosyl radical; competitive inhibition of the catalytic site