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)
- 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 - Premature ovarian insufficiency (POI) is a heterogeneous reproductive disorder, with genetic factors, particularly defects in DNA damage response pathways, increasingly implicated in its pathogenesis. DNA ligase IV (LIG4) is a key enzyme in the non-homologous end joining (NHEJ) pathway responsible for repairing DNA double-strand breaks (DSBs). However, its role in non-syndromic POI remains unclear. This study aimed to investigate the potential contribution of LIG4 variants to non-syndromic POI. - Source: PubMed
Publication date: 2026/06/24
Yu ShaZhou XingyuLai YunhuiTang ShuyanChen Shiling - 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