RNF168 siRNA – E3 Ubiquitin-Protein Ligase RNF168 (Mouse)

RNF168: E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8- dependent H2A ubiquitination, promoting the formation of 'Lys-63'- linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. 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 involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively). Defects in RNF168 are the cause of Riddle syndrome (RIDDLES). Riddle syndrome is characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature. Defects are probably due to impaired localization of TP53BP1 and BRCA1 at DNA lesions. Belongs to the RNF168 family.

Protein type: Ubiquitin conjugating system; EC 6.3.2.-; Ubiquitin ligase

Cellular Component: nucleoplasm; cytoplasm; nucleus; ubiquitin ligase complex

Molecular Function: ubiquitin binding; zinc ion binding; histone binding; coenzyme F420-2 alpha-glutamyl ligase activity; UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanine ligase activity; metal ion binding; nucleosome binding; ribosomal S6-glutamic acid ligase activity; ubiquitin-protein ligase activity; chromatin binding; coenzyme F420-0 gamma-glutamyl ligase activity; ligase activity

Biological Process: ubiquitin-dependent protein catabolic process; positive regulation of DNA repair; double-strand break repair; isotype switching; protein ubiquitination; chromatin modification; response to ionizing radiation; DNA repair; response to DNA damage stimulus