XRCC4 MaxPab Antibody
- Known as:
- XRCC4 MaxPab Antibody
- Catalog number:
- ENZ-007518-B01
- Product Quantity:
- 0.05ml
- Category:
- -
- Supplier:
- Zyagen
- Gene target:
- XRCC4 MaxPab Antibody
Related genes to: XRCC4 MaxPab Antibody
- Gene:
- XRCC4 NIH gene
- Name:
- X-ray repair cross complementing 4
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 5q14.2
- Locus Type:
- gene with protein product
- Date approved:
- 1990-10-16
- Date modifiied:
- 2016-06-02
Related products to: XRCC4 MaxPab Antibody
Related articles to: XRCC4 MaxPab Antibody
- Lung cancer management remains constrained by a fragmented understanding of the clinical implications of DNA Damage Response (DDR) pathways. This review synthesizes current evidence to position DDR alterations as potential prognostic, predictive, and therapeutic biomarkers. Prognostically, overexpression of FEN1, BRCA1, and XRCC4/5/6 correlates with poor survival in non-small cell lung cancer, whereas low ERCC1 expression and specific EXO1 or RPA polymorphisms are associated with enhanced responsiveness to platinum-based chemotherapy. As well, deleterious mutations in ATM, ERCC family genes, and mismatch repair genes (MSH2, PMS2) may support the identification of patients more likely to benefit from immune checkpoint inhibitors, driven by increased tumor mutational burden and neoantigen load. Therapeutically, PARP and ATR inhibitors may offer an opportunity within precision strategies through synthetic lethality, with particular promise in difficult-to-treat subsets, including KRAS-mutated adenocarcinoma and patients progressing on standard targeted therapies. However, clinical implementation faces significant technical limitations regarding testing variability (particularly isoform specificity), geographic biases toward Asian populations, and severe overlapping toxicities in combination trials. To facilitate the integration of DDR biomarkers into routine practice, future research must prioritize assay standardization, broader ethnic representation, and mechanistic exploration of DDR-mediated remodeling of the tumor microenvironment. Integrating these complex molecular interactions is essential to bridge the gap between biological activity and personalized clinical application in lung cancer. - Source: PubMed
Publication date: 2026/08/15
Durán-Toribio Ana-KarlaJiménez-Díaz Ignacio FCaballé-Pérez EnriqueLucio-Lozada JoséCastillo-Ruiz CesarBarrios-Bernal PedroRomero-Núñez EuniceHernández-Pedro NormaArrieta Oscar - Ataxia Telangiectasia Mutated (ATM) kinase deficiency results in cancer susceptibility and drug hypersensitivity. Deficiency in either the BRCA1 interacting A complex or XRCC4/Ligase 4 confers resistance to Topoisomerase I or PARP1 inhibitors in ATM-deficient cells. This suggests that BRCA1-A directs toxicity to fork-damaging agents in ATM mutated cells via illegitimate end-joining. Here, we show that ATM inhibition triggers combined SUMO and ubiquitin mediated BRCA1-A damaged fork recognition to restrict end-resection and cause Topoisomerase I inhibitor hypersensitivity. BRCA1-A deficient cells display elevated chromatin accessibility and nuclease activity at damaged forks, coupled with restored resection and drug resistance. Electron microscopy evidence demonstrates that ATM inhibition prevents replication fork reversal, which is restored by BRCA1-A loss to generate substrates for end resection. These findings reveal that BRCA1-A enforces a restrictive chromatin state to suppress the genesis of resection substrates, implicating fork reversal as a key determinant of chemotherapy response in ATM deficient cells. - Source: PubMed
Publication date: 2026/07/04
Datta ArindamJackson JessicaMorozov Yaroslav IQiu JinghanVindigni AlessandroGreenberg Roger A - 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 - Posttranslational modifications with ubiquitin-like modifiers (UBLs) are critical for genome maintenance, yet many remain mechanistically uncharacterised. Here, we identify UFM1 as a key regulator of non-homologous end-joining (NHEJ), a major DNA double-strand break repair pathway. Using a structure-guided chemical biology approach, we develop a photo-crosslinkable UFM1 probe and, in combination with NMR, map non-canonical UFM1-binding interfaces in core NHEJ factors, including the disordered XRCC4 tail. Mechanistically, proximity-dependent proteomics and functional assays identify Ku70 as a crucial UFMylation substrate and reveal a UFM1-dependent axis in which XRCC4 engages UFMylated Ku70 to stabilise NHEJ complex assembly on chromatin. Disruption of this molecular mechanism via UFSP2 depletion or a hypomorphic UBA5 variant in patient-derived cells impairs NHEJ function, linking UFMylation defects to compromised genome integrity processes. Our findings define a complete UFM1 signalling module in DNA repair and establish a generalisable framework for dissecting low-affinity UBL networks with broad functional and disease relevance. - Source: PubMed
Publication date: 2026/06/15
Wang ZijuanFoster Benjamin Mda Costa Isabelle CWu YueBehera DeepakConte FrancescaTrotter Eleanor WLopezcolorado Felicia WednesdayCabello-Lobato Maria JoseChoudhary ShwetaWiener ReuvenBeli PetraSmith Duncan LBanks William HBagley StevenMcKee ShaneMinnis MeenakshiMeyer StefanChaplin Amanda KDörner WolfgangMootz Henning DHagan Iain MGalanty YaronStark Jeremy MLarrosa IgorCliff Matthew JSchmidt Christine K