RNF168
Description
The RNF168 (ring finger protein 168) is a protein-coding gene located on chromosome 3.
RNF168, also known as RING finger protein 168 or RING-type E3 ubiquitin transferase RNF168, is a human gene encoding an E3 ubiquitin-protein ligase crucial for DNA damage repair. It's responsible for concentrating repair proteins at DNA damage sites. RNF168 amplifies RNF8-dependent histone ubiquitination, promoting the recruitment of crucial repair proteins like TP53BP1 and BRCA1. RNF168 is also involved in DNA interstrand cross-link repair and class switch recombination in the immune system.
RNF168 is an E3 ubiquitin ligase that plays a crucial role in DNA damage repair by accumulating repair proteins at the sites of damage. It works in conjunction with UBE2N/UBC13 to enhance histone ubiquitination initiated by RNF8. RNF168 binds to ubiquitinated histones H2A and H2AX at double-strand breaks (DSBs), amplifying H2A ubiquitination, which facilitates the formation of 'Lys-63'-linked ubiquitin conjugates. This process concentrates ubiquitinated histones at DNA lesions, triggering the recruitment of TP53BP1 and BRCA1 for DNA repair. RNF168 is also recruited to interstrand cross-links (ICLs) sites, where it promotes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to the recruitment of FAAP20/C1orf86 and the Fanconi anemia (FA) complex, ultimately repairing ICLs. Furthermore, RNF168 contributes to ATM-dependent transcriptional silencing in the vicinity of DSBs, preventing collisions between transcription and repair mechanisms. RNF168 is also involved in class switch recombination in the immune system through its regulation of DSBs repair. In the aftermath of DNA damage, RNF168, in collaboration with RNF8, ubiquitinates and degrades JMJD2A/KDM4A, revealing the H4K20me2 mark and promoting TP53BP1 recruitment to damaged DNA. While RNF168 cannot initiate 'Lys-63'-linked ubiquitination in vitro, potentially due to partial obstruction of the UBE2N/UBC13 binding site, it catalyzes the monoubiquitination of 'Lys-13' and 'Lys-15' residues on nucleosomal histone H2A, generating H2AK13Ub and H2AK15Ub, respectively. RNF168 exists as a monomer and interacts with UBE2N/UBC13.
RNF168 is also known as RIDL, hRNF168.
