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
Histone ubiquitylation has emerged as an important chromatin modification associated with DNA damage signaling and repair pathways.These histone marks,laid down by E3 ubiquitin ligases that include RNF8 and RNF168,dec...Histone ubiquitylation has emerged as an important chromatin modification associated with DNA damage signaling and repair pathways.These histone marks,laid down by E3 ubiquitin ligases that include RNF8 and RNF168,decorate chromatin domains surrounding DNA double-strand breaks(DSBs).Recent work implicated ubiquitylated histones in orchestrating cell cycle checkpoints,DNA repair and gene transcription.Here we summarize recent advances that contribute to our current knowledge of the highly dynamic nature of DSB-associated histone ubiquitylation,and discuss major challenges ahead in understanding the versatility of ubiquitin conjugation in maintaining genome stability.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.
基金supported by Faculty Development Fund and Seed Funding for Applied Research to MSYH(No.201007160001).
文摘Histone ubiquitylation has emerged as an important chromatin modification associated with DNA damage signaling and repair pathways.These histone marks,laid down by E3 ubiquitin ligases that include RNF8 and RNF168,decorate chromatin domains surrounding DNA double-strand breaks(DSBs).Recent work implicated ubiquitylated histones in orchestrating cell cycle checkpoints,DNA repair and gene transcription.Here we summarize recent advances that contribute to our current knowledge of the highly dynamic nature of DSB-associated histone ubiquitylation,and discuss major challenges ahead in understanding the versatility of ubiquitin conjugation in maintaining genome stability.
