DNA damage response(DDR) is essential for maintaining genome stability and protecting cells from tumorigenesis. Ubiquitin and ubiquitin-like modi?cations play an important role in DDR, from signaling DNA damage to med...DNA damage response(DDR) is essential for maintaining genome stability and protecting cells from tumorigenesis. Ubiquitin and ubiquitin-like modi?cations play an important role in DDR, from signaling DNA damage to mediating DNA repair. In this report, we found that the E3 ligase ring ?nger protein 126(RNF126) was recruited to UV laser micro-irradiation-induced stripes in a RNF8-dependent manner. RNF126 directly interacted with and ubiquitinated another E3 ligase, RNF168. Overexpression of wild type RNF126, but not catalytically-inactive mutant RNF126(CC229/232 AA), diminished ubiquitination of H2 A histone family member X(H2AX),and subsequent bleomycin-induced focus formation of total ubiquitin FK2, TP53-binding protein1(53 BP1), and receptor-associated protein 80(RAP80). Interestingly, both RNF126 overexpression and RNF126 downregulation compromised homologous recombination(HR)-mediated repair of DNA double-strand breaks(DSBs). Taken together, our ?ndings demonstrate that RNF126 negatively regulates RNF168 function in DDR and its appropriate cellular expression levels are essential for HR-mediated DSB repair.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos.31530016 and 31761133012)the National Basic Research Program of China (Grant Nos.2015CB910601 and 2017YFA0503900)the Shenzhen Science and Technology Innovation Commission (Grant No.JCYJ20170412113009742 awarded to XX),China
文摘DNA damage response(DDR) is essential for maintaining genome stability and protecting cells from tumorigenesis. Ubiquitin and ubiquitin-like modi?cations play an important role in DDR, from signaling DNA damage to mediating DNA repair. In this report, we found that the E3 ligase ring ?nger protein 126(RNF126) was recruited to UV laser micro-irradiation-induced stripes in a RNF8-dependent manner. RNF126 directly interacted with and ubiquitinated another E3 ligase, RNF168. Overexpression of wild type RNF126, but not catalytically-inactive mutant RNF126(CC229/232 AA), diminished ubiquitination of H2 A histone family member X(H2AX),and subsequent bleomycin-induced focus formation of total ubiquitin FK2, TP53-binding protein1(53 BP1), and receptor-associated protein 80(RAP80). Interestingly, both RNF126 overexpression and RNF126 downregulation compromised homologous recombination(HR)-mediated repair of DNA double-strand breaks(DSBs). Taken together, our ?ndings demonstrate that RNF126 negatively regulates RNF168 function in DDR and its appropriate cellular expression levels are essential for HR-mediated DSB repair.
