Ask about this productRelated genes to: RNF168 antibody
- Gene:
- RNF168 NIH gene
- Name:
- ring finger protein 168
- Previous symbol:
- -
- Synonyms:
- FLJ35794
- Chromosome:
- 3q29
- Locus Type:
- gene with protein product
- Date approved:
- 2005-01-25
- Date modifiied:
- 2019-04-23
Related products to: RNF168 antibody
Related articles to: RNF168 antibody
- RAG endonuclease initiates V(D)J recombination by cleaving recombination signal sequences (RSSs), subsequently repaired by classical nonhomologous end-joining (c-NHEJ). However, 53BP1, as a key DNA damage response (DDR) factor promoting c-NHEJ, is dispensable for V(D)J recombination. Here, we report that 53BP1 orchestrates sequence strength of RAG targets to shape end-joining features during V(D)J recombination. Loss of 53BP1, rather than other DDR factors, specifically increases junctional microhomology (MH) of cryptic RSS (cRSS) recombination instead of RSS recombination. This phenotype is partially recapitulated by RIF1 or Shieldin depletion, implicating the 53BP1-mediated end-joining axis. Notably, loss of RNF168, rather than other classical resection and alternative end-joining factors, fully reverts 53BP1 deficiency-mediated increase of junctional MH during cRSS recombination. RAG mutant and RSS score analyses indicate that the sequence strength of RAG targets dictates the unique roles of 53BP1 in balancing end-joining outcomes. Our findings provide deeper mechanistic insights into DNA damage repair at RAG-cleaved on- and off-targets during V(D)J recombination. - Source: PubMed
Publication date: 2026/05/22
Luo ShaZha HailiangYang ZifanLi ShuchanYu LeyiQiao RuolinKong RuoxiWang YifanGuan JunhongZhang Xuefei - Aberrantly enhanced DNA damage repair contributes to therapy resistance and poor prognosis in nasopharyngeal carcinoma (NPC), but its regulatory mechanisms remain unclear. Stress granules (SGs) mediate tumor stress adaptation, yet their role in NPC DNA damage repair is unknown. Here, we show that SGs are significantly enriched in NPC cells under stress, and the SG core protein G3BP1 is highly expressed in NPC tissues (n = 111), correlating with metastasis and poor survival. Mechanistically, under stress, N-acetyltransferase 10 (NAT10)-catalyzed N4-acetylcytosine (ac4C) modification targets mRNAs of DNA repair genes (ATF3, LIG1, RNF168) to SGs, protecting them from degradation. Upon stress relief, these mRNAs are released for translation, enhancing DNA damage repair. The G3BP1/NAT10/ATF3 axis is critical for NPC DNA repair and metastasis, as blocking this axis (via G3BP1 depletion, NAT10 inhibitor remodelin, or ATF3 knockout) inhibits tumor growth and metastasis in vitro and in vivo. This study uncovers a novel ac4C-dependent mechanism by which SGs regulate DNA damage repair in NPC, identifying the G3BP1/NAT10/ATF3 axis as a potential therapeutic target for improving NPC prognosis. - Source: PubMed
Publication date: 2026/04/24
Yue TianYin HaimengYuan LingXie XinchengXie HaijingGong MengfangXu XianSun ChunxiaoZhang KaiwenLiu Jisheng - The molecular mechanisms driving SLFN11 chromatin recruitment remain partially elucidated. Using high-throughput imaging of 162 oncology-focused compounds in U2OS cells with inducible SLFN11 expression, we discovered that deubiquitinase (DUB) inhibitors drive massive SLFN11 recruitment to chromatin, preferentially at promoter regions while concurrently suppressing transcription. DUB inhibitors such as VLX-1570 promote ubiquitin-dependent enrichment of SLFN11 without detectable DNA damage, distinct from the camptothecin-induced RPA-associated SLFN11 foci formed at stressed replication forks. Yet, SLFN11 chromatin recruitment both by DUB inhibitors and DNA damage are suppressed by TAK243 demonstrating their ubiquitylation dependency. RNF168 is required for SLFN11 ubiquitylation and its subsequent chromatin association, and ubiquitylation within SLFN11's middle linker domain (lysines 390, 391, and 429) with K27-linked polyubiquitin chains is essential for the chromatin recruitment of SLFN11. These findings suggest the importance of SLFN11 ubiquitylation by RNF168 for SLFN11 chromatin recruitment and SLFN11 transcriptional regulatory role at promoter regions. - Source: PubMed
Publication date: 2026/04/10
Taniyama DaikiPegoraro GianlucaWu YingHuang Shar-Yin NaomiThomas Craig JOzbun LaurentTran Andy DSaha Liton KMurai JunkoJo UkhyunPommier Yves - The molecular mechanisms driving SLFN11 chromatin recruitment remain partially elucidated. Using high-throughput imaging of 162 oncology-focused compounds in U2OS cells with inducible SLFN11 expression, we discovered that deubiquitinase (DUB) inhibitors drive massive SLFN11 recruitment to chromatin, preferentially at promoter regions while concurrently suppressing transcription. DUB inhibitors such as VLX-1570 promote ubiquitin-dependent enrichment of SLFN11 without detectable DNA damage, distinct from the camptothecin-induced RPA-associated SLFN11 foci formed at stressed replication forks. Yet, SLFN11 chromatin recruitment both by DUB inhibitors and DNA damage are suppressed by TAK243 demonstrating their ubiquitylation dependency. RNF168 is required for SLFN11 ubiquitylation and its subsequent chromatin association, and ubiquitylation within SLFN11's middle linker domain (lysines 390, 391, and 429) with K27-linked polyubiquitin chains is essential for the chromatin recruitment of SLFN11. These findings suggest the importance of SLFN11 ubiquitylation by RNF168 for SLFN11 chromatin recruitment and SLFN11 transcriptional regulatory role at promoter regions. - Source: PubMed
Publication date: 2026/03/26
Taniyama DaikiPegoraro GianlucaWu YingHuang Shar-Yin NaomiThomas Craig JOzbun LaurentTran Andy DSaha Liton KMurai JunkoJo UkhyunPommier Yves - V(D)J recombination is the fundamental process by which developing T and B lymphocytes generate diverse antigen receptors, enabling adaptive immunity. This tightly regulated program operates exclusively in lymphoid precursors during G1 phase and depends on the lymphocyte specific RAG1-RAG2 recombinase to introduce programmed DNA double-strand breaks at recombination signal sequences, followed by repair through the classical non-homologous end-joining (c-NHEJ) pathway. Disruption of any step in this molecular choreography compromises antigen receptor diversity and underlies a spectrum of inborn errors of immunity (IEI), ranging from severe combined immunodeficiency (SCID) to immune dysregulation with autoimmunity and granulomatous disease. In this review, we place disorders of V(D)J recombination within the broader framework of T-cell development, detailing the temporal waves of recombinase activity, chromatin accessibility, and DNA damage responses that guide thymocyte differentiation. We discuss pathogenic variants affecting the cleavage phase (RAG1, RAG2, and the recently identified RAG co-chaperone NudC domain-containing 3, NUDCD3), end processing (ARTEMIS), ligation and repair (LIG4, XLF, XRCC4, PRKDC), and genome surveillance pathways (ATM, MRN complex, RNF168), highlighting genotype-phenotype correlations and mechanisms driving immune deficiency and dysregulation. We briefly review recent diagnostic advances, including newborn screening using T-cell receptor excision circles, repertoire sequencing, and functional assays, alongside current therapeutic strategies. Finally, we outline key unanswered questions and argue that continued integration of clinical observation with molecular discovery is essential to improve outcomes and deepen understanding of adaptive immune development. - Source: PubMed
Publication date: 2026/03/28
Schim van der Loeff InaAhuja ManishaChen RuiPatane EleonoraHambleton Sophie