E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: 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 remove target proteins from DNA damage sites. Following DNA DSBs, it is 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 formation of tp53bp1 and brca1 ionizing radiation-induced foci (IRIF). H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains, leading to degradation of substrate proteins. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of the rnf8 homodimer and a E2 heterodimer of ube2n and ube2v2. Following DNA double-strand breaks, recruited to the sites of damage. The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1. Belongs to the RNF8 family.