Human Polyclonal LIG4 Ab
- Known as:
- Human Polyclonal LIG4 Antibody
- Catalog number:
- a1743
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- ABclonal
- Gene target:
- Human Polyclonal LIG4
Related genes to: Human Polyclonal LIG4 Ab
- 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: Human Polyclonal LIG4 Ab
Related articles to: Human Polyclonal LIG4 Ab
- The DNA damage response (DDR) is a complex network of cellular pathways that ensures the faithful maintenance of our genomes upon a wide array of genomic insults. To elucidate the functional architecture of this network, we conducted unbiased genetic interaction screens using the Cas12a genome editor to disrupt 233 DDR genes frequently mutated in cancer and other genetic diseases, either individually or in pairwise combinations. This approach enabled us to assess the phenotypic effects induced by the disruption of >27,000 DDR gene pair combinations under unperturbed cell growth conditions. From this analysis, we identified over 750 high-confidence positive (buffering) or negative (synthetic lethal/sick) gene-gene interactions, along with multiple connections between previously unlinked DDR pathways and modules, allowing us to define novel aspects of the cellular response to spontaneous, DNA replication-associated DNA damage. Among the identified genetic interactions, we uncovered profound synthetic lethal interactions between genes encoding 1) the translesion polymerase REV1-Pol ζ complex and the MCM8-MCM9-HROB DNA helicase complex; 2) Fanconi Anemia (FA) proteins and the mitotic DNA repair factors GEN1, CIP2A, and RHINO; and 3) the DNA translocase SMARCAL1 and components of the FANCM complex, suggesting novel opportunities for targeted therapies in tumors carrying mutations in these genes. Additionally, we identified robust suppressor interactions between the gene encoding the nuclease APOLLO and the core non-homologous end joining (NHEJ) genes , , and , suggesting that NHEJ impairs the fitness of APOLLO-deficient cells. This work provides a functional map of the DDR network and demonstrates the power of Cas12a-based screens for identifying synthetic lethal and buffering interactions with therapeutic potential. - Source: PubMed
Publication date: 2026/06/08
Hayward Samuel BVaitsiankova AlinaLama-Diaz TomasChou JuihsuanTaglialatela AngeloHuang Jen-WeiWijesekarahanthi YodharaudshaniHeyza Joshua RLeuzzi GiuseppeChen ChuanyuanWong NancyLhakhang TenzinFu XiBuendia Alejandro LGheorghe VeronicaAnvar Nazanin EsmaeiliSchmidt Jens CNussenzweig AndreRabadan RaulCostanzo VincenzoGuérois RaphaëlHart TraverCiccia Alberto - Severe combined immune deficiency (SCID) is a rare inherited defect of lymphocytes causing life-threatening opportunistic infections in early infancy. Data on SCID from China are limited. This study explores the clinical, immunologic, and genetic features of a SCID cohort from Yunnan Province in China and reports novel variants. We collated clinical, laboratory, and molecular details from patients with a clinical profile suggestive of SCID. Trio-based whole-exome sequencing was performed to identify genetic variants. For the 9 previously reported variants identified in our cohort, we systematically reviewed the literature for additional cases carrying the same variants and compared clinical and immunologic features. Eleven infant patients (8 males and 3 females) were included. Molecular diagnoses were obtained in 10 patients, as follows: IL2RG (3), RAG2 (3), LIG4 (2), DCLRE1C (1), and CD3D (1). Nine patients presented with classic SCID features within the first 3 months of life. Eleven variants were identified: 2 novel RAG2 variants (p.L469P and p.Q492R) and 9 variants previously reported in SCID-associated genes. One patient with the p.Q492R variant exhibited a relatively milder clinical course. An extremely rare case of Omenn syndrome due to IL2RG deficiency was also observed. Ten of 11 patients died within 6 months of age. The literature review identified 94 additional cases carrying these same variants; clinical presentations were generally consistent with our patients, although some variability was observed. We characterized the clinical and genetic profiles of 11 SCID patients from Yunnan, China, identifying two novel RAG2 variants. While these findings expand the mutational spectrum in understudied populations, the high mortality and diagnostic delays observed here underscore the critical need for universal newborn screening in China. Further functional studies are required to confirm the impact of the identified variants. - Source: PubMed
Publication date: 2026/05/28
Wang YanjunJin RuohongHan QianHang LingLv LingChen GuizhiHu RongXiao Shufang - The development of engineered Chinese Hamster Ovary (CHO) cell lines capable of long-term, stable, and efficient recombinant protein expression is essential for industrial biologics manufacturing. Traditional random integration is hindered by epigenetic silencing and position effects, while current site-specific strategies are restricted by a limited stable library. To address this, we established a screening strategy based on two core criteria for ideal loci: 1) the capacity for sustained exogenous protein expression and 2) minimal impact on host cell physiology. By analyzing chromosomal location and expression data from 52 known stable loci, we identified 3,152 highly expressed genes. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses excluded genes essential for core growth and metabolism, yielding 252 candidate sites. These were further refined to 25 ideal candidate loci by evaluating their betweenness centrality in a protein-protein interaction (PPI) network, prioritizing hubs with potential genomic stability. After 40 generations of continuous culture, the Enhanced Green Fluorescent Protein (EGFP)-positive rates of DNA ligase 4-like protein (LIG4), L-threonine 3-dehydrogenase, mitochondrial (LOC100759874), and alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS), remained above 95%. This study established an orthogonal functional enrichment screening strategy, which significantly improved the discovery efficiency of stable expression sites in CHO cells and laid a foundation for constructing highly stable recombinant cell lines suitable for industrial production. - Source: PubMed
Publication date: 2026/05/26
Liu YazhouDing XuefengMou LuLi XuerouCai YanfeiZhang LinpeiJin JianChen Yun - Viral polymerases are key targets for antiviral drug development due to their crucial role in viral replication. This study seeks to discover novel inhibitors using virtual screening of a 200,583-member ZINC-based library, targeting three aspartyl-based viral polymerases: SARS-CoV-2 RdRp, HIV-1 RT, and HCV NS5B. In this line, applying RO5, drug-likeness, and PAINS filters, leading to a pharmacophore model with Ribavirin as the benchmark. Four ligands (Ligands 1-4) with the highest binding affinities were identified via molecular docking and ADME/T studies. These candidates were then subjected to 200 ns molecular dynamics (MD) simulations and binding free-energy calculations to evaluate binding stability. The computational analyses demonstrated that all four ligands stably bound the polymerase active sites and induced some conformational changes. According to MM/PBSA results, Lig-2 and Lig-1 surpass Ribavirin in SARS-CoV-2 RdRp and HIV-1 RT complexes, while Ribavirin showed the strongest binding in HCV NS5B. ADME/T studies supported the pharmacological potential of the ligands, with Lig-2 emerging as a promising lead against all targets, and Lig-1, Lig-3, and Lig-4 showing potential for multi-target antiviral development. - Source: PubMed
Publication date: 2026/05/26
Zarei ArminEzati MohammadMorris Marc TSchenk GerhardAdibi Hadi - Homologous recombination (HR) between sister chromatids is the dominant outcome of replication-associated DNA repair, yet the lesions that initiate spontaneous mitotic crossovers remain poorly defined. Most mechanistic work on HR pathway choice uses enzymatically induced two-ended double-strand breaks (DSBs), where non-homologous end joining (NHEJ) is a major competing pathway. Whether NHEJ also competes for spontaneous, replication-associated lesions has not been directly tested. Here we use sci-L3-Strand-seq, a single-cell replication-template strand-specific sequencing method that maps sister chromatid exchange (SCE) genome-wide, to profile heterozygous and homozygous knockouts of NHEJ factors (LIG4, XRCC4) and the single-strand break (SSB) repair scaffold XRCC1 in HAP1 and BJ cell lines. NHEJ disruption produced only a modest (30%) increase in SCE, whereas XRCC1 loss caused a pronounced, 5-fold elevation. The dense, widespread SCE pattern in XRCC1-deficient cells is consistent with unrepaired SSBs being converted at replication forks into one-ended DSBs that lack a second end for ligation and therefore cannot engage NHEJ. In parallel, structural variation (SV) mapping in the same single cells revealed a strongly non-random landscape dominated by recurrent chromosome losses and clonal expansion, indicating selective pressure and stepwise genome evolution. SCE frequency did not correlate with SV burden or SV-defined subclones, demonstrating that error-free recombination and mutational rearrangement represent separable axes of genome maintenance. Recovery of reciprocal daughter-cell pairs with matching SCE breakpoints directly confirms that these events arose by inter-sister exchange in the preceding division. Together, these results show that spontaneous mitotic crossovers are driven by lesions largely incompatible with NHEJ and instead engage HR through replication-coupled SSB-to-DSB conversion, and that elevated error-free recombination is decoupled from the mutational SV landscape. - Source: PubMed
Publication date: 2026/05/14
Chovanec PeterHe ShiyangYin Yi