RNF8 Protein, Human (sf9, His, Myc)

RNF8 Protein, an E3 ubiquitin-protein ligase, assumes a pivotal role in DNA damage signaling through two distinct mechanisms: firstly, by catalyzing 'Lys-63'-linked ubiquitination of histones H2A and H2AX to facilitate the recruitment of DNA repair proteins at double-strand break (DSB) sites, and secondly, by promoting 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. In response to DSBs, RNF8 is recruited by ATM-phosphorylated MDC1, leading to the 'Lys-63'-linked ubiquitination of histones and the subsequent formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). It also plays a role in non-homologous end joining (NHEJ) by facilitating the 'Lys-48'-linked ubiquitination and degradation of KU80/XRCC5. Additionally, RNF8 modulates chromatin structure, promoting extensive chromatin decondensation and activating ATM by inducing histone H2B ubiquitination, indirectly triggering histone H4 'Lys-16' acetylation. In the testis, RNF8 contributes to histone replacement during spermatogenesis, and at uncapped telomeres, it induces H2A ubiquitination and TP53BP1 recruitment, potentially exacerbating telomere-induced genome instability. Moreover, RNF8 is implicated in RAD51 assembly at DSBs, class switch recombination in the immune system, proper exit from mitosis, cytokinesis regulation, and may play a role in the regulation of RXRA-mediated transcriptional activity. This extensive functionality underscores the multifaceted contributions of RNF8 in orchestrating DNA damage responses and maintaining genomic integrity.