Ring Finger Protein 168 (RNF168)

The complex repair response elicited by DNA double-strand breaks (DSBs) includes recruitment of several DNA repair proteins and ubiquitination of H2A-type histones. RNF168 is an E3 ubiquitin ligase critical for DSB repair.

RNF168 was required to sustain conjugated ubiquitin at DSBs. RNF168 assembled at DSBs in an RNF8 -dependent manner and functioned as an E3 ubiquitin ligase that acted with UBC13 (UBE2N) to catalyze formation of lys63-linked ubiquitin conjugates and promote ubiquitination of H2A and H2AX (H2AFX). Ubiquitinated H2A and H2AX in turn mediated accumulation of 53BP1 and BRCA1 at DSBs to promote DSB repair and DNA damage checkpoints. The deduced 571-amino acid protein contains an N-terminal RING finger domain, followed by 2 'motifs interacting with ubiquitin' (MIU) domains.