RNF168 is a RING-type ubiquitin E3 ligases with roles in the DNA damage response to double-strand breaks (DSBs). It works in concert with another RING-type ubiquitin E3 ligase, RNF8, targeting histones H2A and H2AX. RNF168 amplifies the RNF8-dependent H2A ubiquitination of K-63, promoting the formation ubiquitin conjugates that contribute to the ubiquitin-dependent signals necessary for recruitment of downstream regulators of the DSB response pathway [, , , ]. Interestingly, RNF168 also catalyses H2A monoubiquitination on K13-15; this seems to be the first step of H2A ubiquitination that drives the DNA damage signaling [].
