RNF8s

RNF8 is a ubiquitin ligase that plays a crucial role in DNA damage response pathways. It is a key E3 ubiquitin ligase that catalyzes the ubiquitylation of histone H2A and H2B at sites of DNA double-strand breaks. This ubiquitylation is an early and essential step in the recruitment of downstream repair factors, such as MDC1 and RNF168, to the damaged DNA.

The catalytic activity of RNF8 is mediated by its Really Interesting New Gene (RING) domain, which interacts with the E2 ubiquitin-conjugating enzyme Ubc13. RNF8 also contains a forkhead-associated (FHA) domain that is important for its localization to DNA damage sites, often through interaction with phosphorylated proteins like MDC1.

RNF8-mediated ubiquitylation is critical for the efficient repair of DNA double-strand breaks through both homologous recombination and non-homologous end joining pathways. Defects in RNF8 function can lead to genomic instability and an increased susceptibility to cancer. Beyond its role in DNA repair, RNF8 has also been implicated in other cellular processes, including transcriptional regulation and mitosis.