E3 ubiquitin-protein ligase RNF8 (RNF8)

E3 ubiquitin-protein ligase that plays an integral role in DNA damage signaling through 2 different functions: by mediating the'Lys-63'- linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing'Lys-48'-linked ubiquitination to eliminate target proteins from DNA damage sites. Following DNA DSBs, it's recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the creation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF).

Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link restoration.