p53R2

p53R2, also known as the p53-regulated ribonucleotide reductase small subunit and encoded by the RRM2B gene, is a component of the ribonucleotide reductase (RNR) enzyme complex. It serves as an alternative small subunit to the canonical RNR pair and forms a holoenzyme with the large subunit RRM1. The p53R2 subunit enables the conversion of ribonucleotides to deoxyribonucleotides, providing the building blocks required for DNA synthesis and repair, particularly under conditions of DNA damage or cellular stress when the cell is not in active S phase.

Regulation and function of p53R2 are closely linked to the tumor suppressor protein p53. In response to DNA damage, p53 upregulates RRM2B expression, increasing the supply of deoxynucleotides needed for repair processes. This is important not only for nuclear DNA repair but also for maintaining mitochondrial DNA (mtDNA), since mitochondria rely on a cytosolic pool of deoxynucleotides for mtDNA replication and maintenance. The protein is broadly expressed, with activity centered in tissues that require robust DNA repair or mtDNA maintenance.

Clinical significance of RRM2B includes its association with mitochondrial DNA depletion syndromes when mutated. Germline mutations in RRM2B can lead to reduced mtDNA copy number and a spectrum of clinical phenotypes, including neuromuscular and metabolic manifestations. Inheritance is typically autosomal recessive, and disease presentation can range from early-onset multisystem involvement to later-onset features. Ongoing research investigates the precise contributions of p53R2 to DNA repair pathways and mtDNA maintenance, as well as potential therapeutic implications.