E3 ubiquitin-protein ligase RNF8 (RNF8)

E3 ubiquitin-protein ligase RNF8 (RNF8) is an enzyme widely recognized for its critical role in the DNA damage response, acting primarily as a signal transducer in the repair of DNA double-strand breaks (DSBs). RNF8 contains a forkhead-associated (FHA) domain for protein-protein interactions and a RING finger motif that confers ubiquitin ligase activity. It operates by catalyzing the ubiquitination of histones (notably H2A and H2AX) at DNA damage sites, promoting the recruitment of downstream repair proteins (such as BRCA1 and 53BP1) and facilitating chromatin remodeling necessary for efficient repair through homologous recombination and non-homologous end joining pathways[1][3][5][6]. Beyond DNA repair, RNF8 participates in telomere maintenance, cell cycle progression, and transcriptional regulation. Disruption or deficiency of RNF8 causes genomic instability and predisposes to spontaneous tumorigenesis in mouse models and is implicated in human cancer progression and metastasis, partly by influencing transcription factors that contribute to epithelial-mesenchymal transition[1][3][4]. While considered a potential therapeutic target, no direct drugs or inhibitors are clinically validated, but its activity is under investigation, particularly in cancer and inflammatory processes[2][3][4][6].

Other names

RNF8RING finger protein 8KIAA0646hRNF8C3HC4-type zinc finger proteinUBC13/UEV-interacting ring finger proteinRING-type E3 ubiquitin transferase RNF8

Modulation of RNF8 (theoretically or in preclinical studies) would alter DNA repair capacity, histone ubiquitination, chromatin remodeling, and the recruitment of DNA repair complexes.