LIG4 Antibody (OAAF03014)
- Known as:
- LIG4 Antibody (OAAF03014)
- Catalog number:
- oaaf03014
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- LIG4 Antibody (OAAF03014)
Related genes to: LIG4 Antibody (OAAF03014)
- Gene:
- LIG4 NIH gene
- Name:
- DNA ligase 4
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 13q33.3
- Locus Type:
- gene with protein product
- Date approved:
- 1995-08-10
- Date modifiied:
- 2019-04-23
Related products to: LIG4 Antibody (OAAF03014)
Related articles to: LIG4 Antibody (OAAF03014)
- Glioblastoma (GBM), the deadliest primary brain malignancy, resists treatment because of the blood‒brain barrier (BBB) and intrinsic resistance mechanisms. Fluorescein (FL), a clinically approved fluorophore, shows promise as a sonosensitizer for sonodynamic therapy (SDT), but faces challenges in tumor delivery and incomplete mechanistic understanding beyond ROS-mediated damage. We developed a bioinspired platelet-based delivery platform exploiting the natural tumor-homing properties of platelets for targeted FL delivery. Platelets were loaded with fluorescein diacetate (FDA), a lipophilic prodrug that is converted intracellularly to active FL, combined with probenecid to inhibit MRP1-mediated efflux, generating the ultrasound-responsive FL@plt. In vitro, FL demonstrated sonocytotoxicity; upon low-intensity ultrasound, FL@plt rapidly released FL into GBM cells, producing significant cytotoxicity enhanced by probenecid-mediated retention. In subcutaneous and orthotopic mouse models, intravenous FL@plt with probenecid and sequential ultrasound achieved extensive tumor FL accumulation, massive necrosis, significant growth inhibition, and prolonged survival. Mechanistically, FL-SDT induces DNA damage while promoting HIF-1α degradation via the ubiquitin‒proteasome and autophagy‒lysosome pathways, thus suppressing downstream DNA repair enzymes (SMUG1 and LIG4). This dual mechanism combines direct genotoxicity with impaired DNA repair capacity, underlying the potent anti-GBM efficacy. Our platelet-based FL delivery represents a practical, safe, translational therapy for overcoming BBB limitations by disabling HIF-1α-regulated DNA repair. - Source: PubMed
Publication date: 2026/07/29
Guo Yu-XinDeng QingLi KeZhang QuanGuo JieWang Meng-FeiWu Jia-LinLei Hui-MeiChen Yue-YingPu HuanGao Yu-FanXu Yong-HongChen XiaoZhou Qing - Minimal change disease (MCD) is a leading cause of childhood nephrotic syndrome. Endoplasmic reticulum stress (ERS) and autophagy are implicated in its pathogenesis, but the precise mechanisms remain unclear. This study aimed to identify ERS and autophagy-related key genes (ERS-RGs and ARGs) in MCD using bioinformatic and experimental approaches. Transcriptomic data from GSE216841 and GSE246206 were analyzed. ERS-RGs and ARGs were obtained from prior literature. Candidate genes were selected by integrating weighted gene coexpression network analysis and differential expression analysis. Feature genes were identified via protein-protein interaction network analysis and machine learning (Least Absolute Shrinkage and Selection Operator and Boruta). Key genes were validated by expression analysis and receiver operating characteristic evaluation. A multilayer perceptron (MLP) model was constructed, and regulatory networks, immune infiltration, and chemical compound prediction were analyzed. The expression levels of the identified key genes were preliminarily assessed in peripheral blood samples using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). and were identified as key genes, both significantly downregulated in the MCD group, and the gene-based MLP model effectively predicted MCD probability. Overall, 13 significantly different immune cell types (e.g., CD56 natural killer and activated dendritic cells) were detected. Regulatory networks (transcription factor-messenger RNA (mRNA) and long non-coding RNA-microRNA-mRNA) and 8 common chemical compounds (e.g., bisphenol A, acetaminophen) targeting these genes were predicted. Notably, peripheral blood RT-qPCR analysis revealed significant and downregulation, suggesting a systemic expression signature. and are key genes associated with ERS and autophagy in MCD, providing insights for diagnosis and targeted therapy. - Source: PubMed
Publication date: 2026/06/29
Jiang NingChen GuoqiangXie YunZhang Xiaofei - - Source: PubMed
Publication date: 2026/07/25
Hoshino AkihiroWakatsuki RyosukeWatanabe RyoheiMiyamoto SatoshiKamiya TakahiroIsoda TakeshiImai KohsukeKajiwara MichikoTakagi MasatoshiKanegane Hirokazu - The Mitotic Deacetylase Complex (MiDAC) plays a crucial role in the DNA damage response (DDR), yet the mechanism of its recruitment to double-strand breaks (DSBs) remains poorly unclear. In this study, we identify Poly(ADP-ribose) polymerase 1 (PARP1) as the key factor that directs MiDAC to DSB-proximal chromatin. We demonstrate that this process depends on the physical presence of PARP1, but not its poly(ADP-ribosyl)ation (PARylation) activity. Specifically, the dimerization domain of the MiDAC subunit DNTTIP1 interacts directly with PARP1. Disrupting this interaction prevents MiDAC recruitment and impairs the deacetylation of histone H2A at lysine 5 and 9 (H2AK5ac/K9ac) at damage sites. This leads to genome instability, characterized by an increase in γH2AX foci, accumulation of DNA damage, and chromosomal breaks. The PARP1-DNTTIP1 interaction is mechanistically essential for the assembly of the non-homologous end joining (NHEJ) synaptic complex, as evidenced by a defective KU80-LIG4 interaction and impaired NHEJ efficiency when this interaction is disrupted. Consequently, this interaction is critical for physiological processes that rely on NHEJ, such as immunoglobulin class switch recombination (CSR) in B cells. Our findings establish the PARP1-DNTTIP1 axis as a critical PARylation-independent regulator of MiDAC, linking the sensing of early DNA damage to the subsequent remodeling of chromatin and the efficient repair of DSBs. - Source: PubMed
Publication date: 2026/07/16
Qin YanMa YanhuiWei AoZhang ZhaoBao PeidaJia ShaoweiZhou MengyuLiu LingYang ZhenzhenShi LeiBao Kaiwen - Chromosomal DNA double-strand breaks (DSBs) are repaired by two fundamentally different mechanisms: homologous recombination (HR) and nonhomologous end joining (NHEJ). While NHEJ requires the Ku70-Ku80 heterodimer (Ku) and DNA ligase IV (LIG4), recent work has established a Ku/LIG4-independent mechanism for DSB joining, referred to as alternative end-joining or theta-mediated end-joining (TMEJ). Cells lacking NHEJ and TMEJ repair DSBs in a homology-dependent manner. Here we show that APOBEC3G (A3G), a cytoplasmic antiviral protein that possesses cytidine deaminase activity on ssDNA and inhibits the replication of various types of viruses such as HIV, affects DSB repair in the human lymphocyte cell line Nalm-6. We observed that genetic deletion of A3G in LIG4-null cells resulted in (a) reduced sensitivity to replication-dependent as well as -independent DSBs, (b) enhanced frequency of HR in chromosomal and extrachromosomal reporter assays, and (c) increased frequency of TMEJ-dependent random integration as well as HR-mediated targeted integration (gene targeting). Our results suggest that human A3G, albeit mainly cytoplasmic, acts to suppress HR and TMEJ during DSB repair, particularly when NHEJ is compromised. - Source: PubMed
Publication date: 2026/07/06
Saito ShintaMurayama MioriArai UsakiAkatsu SekifumiYamamoto AmiKadoguchi MisakiAdachi Noritaka