Ask about this productRelated genes to: NHEJ1 antibody
- Gene:
- NHEJ1 NIH gene
- Name:
- non-homologous end joining factor 1
- Previous symbol:
- -
- Synonyms:
- Cernunnos, XLF, FLJ12610
- Chromosome:
- 2q35
- Locus Type:
- gene with protein product
- Date approved:
- 2006-03-30
- Date modifiied:
- 2019-04-23
Related products to: NHEJ1 antibody
Related articles to: NHEJ1 antibody
- External stressors, particularly heat stress, induce DNA damage and genomic instability in cells. However, the mechanisms by which cells rapidly respond to such DNA damage remain largely unknown. In this study, we found that heat shock factor 1 (HSF1), the major transcription factor in the heat shock response, activated several non-homologous end joining (NHEJ) pathway-associated genes, particularly NHEJ1, through puncta formation, thereby maintaining the stability of NHEJ pathway and alleviating the repair burden of DNA double-strand breaks caused by heat stress. Furthermore, N6-methyladenosine (m6A) RNA modification and its reader YTH domain-containing protein 1 (YTHDC1) contributed to this process by promoting the splicing of NHEJ1. Knockdown of HSF1 or YTHDC1 increased nuclear intensity of phosphorylation of histone variant H2AX at Ser-139 (γH2AX) in heat-stressed cells, whereas NHEJ1 overexpression rescued this effect. Moreover, HSF1 or YTHDC1 overexpression increased NHEJ repair efficiency in heat-stressed cells, supporting the existence of an HSF1/YTHDC1-NHEJ1-DNA double-strand repair axis. Our findings reveal a mechanism by which cells repair DNA damage during the heat shock response, providing new insights into how cells maintain genomic stability under external stress conditions. - Source: PubMed
Ding WenqingDeng QidongWang TianyuLiu RuoqianXiang YunfanHuang LuluLiu Jun - Comprehensive molecular and phenotypic characterization of tumor models is still needed for a robust understanding of breast cancer mechanisms and therapies. Here, we explore the genome, transcriptome, and proteome of treated and untreated 4T1 triple-negative breast cancer cells to integrate genomic vulnerabilities and mutational profiling with novel treatment-induced delivery, signaling, and apoptotic responses. Nanoencapsulation (AuNPs) of berry-derived polyphenolic compounds was influenced by limited clinical use due to poor stability and bioavailability. Several physicochemical characterizations employed include TEM, FTIR, and targeted UPLC/MS-QQQ assays. We identified significant mutations to breast cancer-related tumor suppressor genes (TP53, BRCA2, BARD1, CDH1, NF1, and CHEK2) and deciphered the functional consequences leveraging the higher throughput Illumina NovaSeq X and NextSeq sequencing and the highly accurate predictive power of AlphaFold. We found ~5,700,000 single-nucleotide variations (SNVs) and 329448 indels, achieving an important upgrade over existing literature data. Multiple sequence alignment with WT mouse and human protein sequences demonstrated that mutations present in 4T1 cells are within highly conserved motifs of key tumor suppressors, emphasizing their relevance to human breast cancer biology. Key findings from differentially expressed gene enrichment analyses (GSEA) revealed positive gene enrichments of DNA repair regulators and TGF-β signaling, while having negative enrichments of cell adhesion, cadherin and MAPK signaling via PI3K/AKT/MAPK/Wnt pathways, potentially influencing apoptosis and immune evasion intrinsic to cancer. Notably, decreased expression of PIK3CG, PALLD, PTPRZ1, and CDH8 and increased expression of SEMA6C, WWOX, NHEJ1, and MAML3 suggested suppression of epithelial-to-mesenchymal transition (EMT) and metastatic potential. Further assessment of immunohistochemical, immunofluorescent, and flow cytometric data revealed that berry-derived nanoparticles are associated with the modulation of oncogenic transcription factors and linked to induced caspase-dependent execution-phase ROS-mediated apoptosis through pPAK1 dephosphorylation, downregulation of pPI3K/pAKT1/mTOR signaling, and modulation of pJAK3/STAT3 pathway supporting transcriptomic and transcriptional reprogramming of 4T1 treated cells. Together, our findings uncover a new strategy to capture berry-derived polyphenols required to regulate apoptosis, autophagy, immune response, and metastasis-related gene networks in breast cancer, thereby underscoring the therapeutic potential of functionalized AuNPs as delivery platforms for dietary phytochemicals. - Source: PubMed
Publication date: 2026/04/10
Fagbohun Oladapo FOladipo Adewale OGao ChengyuOlawoye BabatundeBerry Rachel SCaptain Jaylah CIragena OliveMcDougle XavierHarris Randy JRollins AmandaJoseph Jitcy SFadare Olatomide AKincaid Russell - Severe combined immunodeficiency (SCID) is a congenital immunodeficiency characterized by significant numerical or functional defects in T lymphocytes and is often accompanied by B lymphocyte dysfunction. It presents early in life with severe, recurrent opportunistic infections. Early diagnosis and hematopoietic stem cell transplantation (HSCT) are vital for patient survival. Cernunnos/XLF deficiency is an autosomal recessive form of SCID caused by mutations in the NHEJ1 gene, which plays a critical role in repairing DNA double-strand breaks. First described in 2006, this condition remains exceedingly rare, with only about 55 cases reported to date. This study aimed to describe a novel infant with Cernunnos/XLF deficiency and to review previously reported patients carrying the same variant, thereby expanding the clinical spectrum of this rare disease. - Source: PubMed
Publication date: 2025/11/12
Kabadayı GizemAtay ÖzgeBaysal Bakır DamlaYağmur HalimeKaşıkçı Mermer Esma TuğbaOkur Acar SultanÖztürk Yılmaz ŞerifeHazan FilizGözmen SalihUzuner Nevin - Metabolic reprogramming and DNA damage repair are essential in tumorigenesis and chemoresistance, yet their link remains elusive. Here, we show that LDHA deficiency impairs NHEJ and class switch recombination. Additionally, glycolysis-derived lactate promotes XLF lactylation at K288 within its Ku-binding motif (X-KBM) to regulate NHEJ. Mechanistically, DNA damage triggers ATM-mediated GCN5 phosphorylation to increase GCN5-XLF interaction and XLF lactylation, enhancing XLF-Ku80 binding, XLF recruitment to DSBs, and NHEJ efficiency. Cryo-EM structural analysis demonstrates that lactylated X-KBM (laX-KBM) forms a more extensive interface with Ku70/80, inducing conformational changes in the Ku80 vWA domain. XLF lactylation deficiency impairs NHEJ and sensitizes cancer cells to chemotherapy. A specific XLF K288 lactylation peptide inhibitor plus 5-fluorouracil synergistically kills colorectal cancer cells in PDX models with XLF hyperlactylation. These findings highlight that the GCN5-XLF lactylation axis is a critical NHEJ regulator and that targeting XLF lactylation can improve chemotherapy efficiency. - Source: PubMed
Jin MingpengHuang BingsongYang XiaoningWang ShuyangWu JinhuanHe YimingDing XinWang XuanheWang ZheYang JieLi RuiZhou XuanWang QianwenLi YunhuiLi LeiZheng WenZeng ZhikaiZhao ChenxiLiu JiaqiZhu QianKang ZhihuaLi KeLiang ShikangChen YupingYuan Jian - Nonhomologous end-joining (NHEJ)1 deficiency causes a genome maintenance disorder (GMD), classically associated with severe combined immunodeficiency. Here, we describe two cases of NHEJ1 deficiency presenting with cytopenias. One patient was an adolescent with recurrent cytopenias and frank immunodeficiency that evolved into bone marrow failure with myelodysplasia, then chronic myelomonocytic leukemia and ultimately treatment-refractory acute myeloid leukemia. The second patient was a preadolescent with only cytopenias. In both cases, diagnosis was not achieved by sending an inherited BMF syndrome panel because of the omission of NHEJ1. Our cases further emphasize that NHEJ1 deficiency harbors additionally under-recognized hematopoietic implications beyond lymphoid abnormalities, adding to the emerging evidence for coexistent myeloid and lymphoid concerns in GMDs. - Source: PubMed
Publication date: 2025/06/28
Weinstock Nadav IApplegate CarolynPeng LeiKeates-Baleeiro JenniferGamper ChrisPeng Xiao P