XRCC4 Monoclonal Antibody

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Description

Introduction

XRCC4 (X-ray repair cross-complementing protein 4) is a critical scaffold protein in the non-homologous end joining (NHEJ) pathway, essential for repairing DNA double-strand breaks (DSBs) and facilitating V(D)J recombination . The XRCC4 Monoclonal Antibody is a laboratory tool designed to detect endogenous XRCC4 proteins in research and diagnostic settings. This antibody is widely used in Western blot (WB), immunoprecipitation (IP), and immunohistochemistry (IHC) to study DNA repair mechanisms, cellular responses to genotoxic stress, and disease-related mutations .

Antibody Properties

AttributeDetailsSources
Host SpeciesMouse
ClonalityMonoclonal
SpecificityTargets endogenous XRCC4 proteins; detects 38–50 kDa isoforms
PurificationAffinity chromatography
ReactivityHuman; cross-reactivity with mouse/rat in some formulations
ApplicationsWB, IP, IHC, ELISA (limited)
FormulationPBS with 50% glycerol, 0.5% BSA, 0.02% sodium azide
Storage-20°C (long-term); 4°C for short-term use

Target Protein Overview

  • Gene ID: 7518 (human), 108138 (mouse) .

  • Accession Numbers: Swiss-Prot Q13426 (human), Uniprot Q924T3 (mouse) .

  • Function: Binds DNA ligase IV, stabilizes the NHEJ complex, and facilitates DSB repair .

  • Disease Associations: Mutations linked to microcephaly, primordial dwarfism, and radiosensitivity but not immunodeficiency .

DNA Repair and V(D)J Recombination Studies

  • Western Blot: Detects XRCC4 in HEK-293, COLO 320, and MCF-7 cell lysates .

  • Immunoprecipitation: Used to study XRCC4 interactions with DNA ligase IV and Ku proteins .

  • Immunohistochemistry: Validates XRCC4 expression in human breast, colon, and liver cancer tissues .

Functional Analysis of Mutant Variants

  • Radiosensitivity Assays: Monoclonal antibodies assess DSB repair efficiency in XRCC4-deficient M10 cells expressing patient-derived mutants (e.g., V83_S105del, R225X) .

  • Nuclear Localization: GFP-tagged mutants (e.g., R225X, R275X) show cytoplasmic mislocalization in fibroblasts .

Disease-Associated Mutations

MutationPhenotypeRepair DeficiencySource
V83_S105delSevere radiosensitivity; impaired XLF interactionNull/Partial function
R225XUndetectable protein; cytoplasmic localizationPartial function (nuclear?)
D254Mfs*68Reduced radiosensitivity; nuclear localization retainedPartial function
W43R/R161Q/R275XSlight radiosensitivity increase; nuclear localization intactNear-wild-type function

Diagnostic Utility

  • Western Blotting: Confirms XRCC4 protein absence in patient fibroblasts (e.g., R225X) .

  • Epistasis Analysis: Determines genetic interactions with Lig4, XLF, and PAXX in DSB repair .

Product Specs

Buffer
Phosphate Buffered Saline (PBS), pH 7.4, containing 0.02% sodium azide as a preservative and 50% Glycerol.
Form
Liquid
Lead Time
Typically, we can ship the products within 1-3 business days after receiving your order. The delivery timeframe may vary depending on the purchasing method or location. For specific delivery details, please contact your local distributors.
Synonyms
DNA double strand break repair and V(D)J recombination protein XRCC4 antibody; DNA repair protein XRCC4 antibody; SSMED antibody; X ray repair complementing defective repair in Chinese hamster cells 4 antibody; X ray repair cross complementing 4 antibody; X ray repair cross complementing protein 4 antibody; X-ray repair cross-complementing protein 4 antibody; XRCC 4 antibody; XRCC4 antibody; XRCC4_HUMAN antibody
Target Names
XRCC4
Uniprot No.

Target Background

Function
XRCC4 (X-Ray Repair Cross Complementing 4) is a crucial DNA non-homologous end joining (NHEJ) core factor, essential for double-strand break repair and V(D)J recombination. It serves as a scaffold protein, regulating the recruitment of other proteins to DNA double-strand breaks (DSBs). XRCC4 forms alternating helical filaments with NHEJ1/XLF, bridging DNA and acting like a bandage, holding the broken DNA together until it is repaired. This XRCC4-NHEJ1/XLF subcomplex binds to DSB fragments with high diffusivity, effectively bridging two separate DNA molecules and bringing the broken ends close together. The mobility of these bridges ensures accessibility for further processing by other repair factors. XRCC4 plays a vital role in the NHEJ ligation step of broken DNA during DSB repair by directly interacting with DNA ligase IV (LIG4). The LIG4-XRCC4 subcomplex reseals the DNA breaks after gap filling is completed. XRCC4 stabilizes LIG4, regulates its subcellular localization, and enhances its joining activity. The binding of the LIG4-XRCC4 subcomplex to DNA ends depends on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends. XRCC4 promotes the displacement of PNKP from processed strand break termini. Moreover, XRCC4 functions as an activator of the phospholipid scramblase activity of XKR4. Upon caspase-3 (CASP3) cleavage, a form of XRCC4 translocates to the cytoplasm and interacts with XKR4, stimulating its phosphatidylserine scramblase activity and leading to phosphatidylserine exposure on the apoptotic cell surface.
Gene References Into Functions
  1. These data suggest that the level of XRCC4 expression could be used to predict the effects of apoptosis-inducing drugs in cancer treatment. PMID: 29233683
  2. A three-locus model of gene-gene interactions involving OGG1 (rs1052133), ADPRT (rs1136410), and XRCC4 (rs6869366) was associated with a high genotoxic risk in coal miners. PMID: 28992182
  3. The variant rs3734091 was found to be significantly associated with breast cancer, while the rs6869366 variant showed no association. These SNPs may influence breast cancer susceptibility in this Indian population. PMID: 29452234
  4. Results indicate that eNOS and XRCC4 VNTR variants might play a potential role in schizophrenia + nicotine dependence and/or nicotine dependence pathophysiology. PMID: 29050484
  5. Phospho-blocking and -mimicking mutations impact both the stability and DNA bridging capacity of XRCC4/XLF complexes, but without affecting their ability to stimulate LIG4 activity. This finding suggests that phosphorylation may regulate DNA bridging by XRCC4/XLF filaments. PMID: 28500754
  6. This study demonstrates that both ligase IV and XRCC4 may act in concert to modulate the development of glioma. PMID: 27508978
  7. Data suggest that genetic variants of XRCC4 and ERCC1 may independently or jointly affect survival in chemotherapy-treated gastric cancer (GCa) patients by modulating gene expression in the tumors. PMID: 28796378
  8. In a recombinant PNKP-XRCC4-LigIV complex, stable binding of PNKP requires XRCC4 phosphorylation. Only one PNKP protomer binds per XRCC4 dimer. Both the PNKP FHA and catalytic domains contact the XRCC4 coiled-coil and LigIV BRCT repeats. Multipoint contacts between PNKP and XRCC4-LigIV regulate PNKP recruitment and activity within NHEJ. PMID: 28453785
  9. Data suggest that stimulation of Artemis nuclease/DCLRE1C activity by the XRCC4-DNA ligase IV hetero-complex and efficiency of blunt-end ligation are determined by structural configurations at the DNA ends. (XRCC4 = X-ray repair cross complementing 4) PMID: 28696258
  10. This review discusses the various XRCC4 mutations that lead to primordial dwarfism and their impact on non-homologous end joining and V(D)J recombination. PMID: 27169690
  11. XRCC4 expression might have an influence on the results of radiotherapy for patients with esophageal squamous cell carcinoma. PMID: 27338590
  12. Uterine cervical cancer patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others. PMID: 26867665
  13. Frequencies of XRCC4-1394 T/G+G/G genotypes were higher in patients (34%) than the controls (18.7%). The statistical analysis revealed that individuals with the XRCC4-1394 T/G+G/G genotype had an increased risk for autism spectrum disorder (OR = 2.23, 95% CI = 1.10-4.55). PMID: 27064873
  14. Genetic Variations in XRCC4 (rs1805377) are not associated with Hepatocellular Carcinoma in Thai Patients with Hepatitis B Virus Infection. PMID: 26925648
  15. These results suggested the potential usefulness of the phosphorylation status of XRCC4 Ser320 as an indicator of DNA-PK functionality in living cells. PMID: 26666690
  16. Association between insertion/deletion polymorphism in intron 3 of XRCC4 and susceptibility to type I bipolar disorder. PMID: 26484731
  17. For XRCC4 (rs1805377) polymorphism, no difference was found in distribution between the ESCC and control groups. PMID: 26166223
  18. Using dual- and quadruple-trap optical tweezers combined with fluorescence microscopy, we show how human XRCC4, XLF, and XRCC4-XLF complexes interact with DNA in real time. PMID: 27437582
  19. Close alignment of the ends requires XLF, a non-catalytic function of XRCC4-LIG4, and DNA-PK activity. PMID: 26990988
  20. Polymorphisms of XRCC4 are associated with susceptibility to Colorectal Cancer. PMID: 25662981
  21. FBXW7 facilitates nonhomologous end-joining via K63-linked polyubiquitylation of XRCC4 in tumor cells. PMID: 26774286
  22. The XRCC4 -1394T/G polymorphism is associated with susceptibility to endometriosis in an Iranian population. PMID: 26088159
  23. Our results suggest that the XRCC4 rs2075685 polymorphism could influence the susceptibility to pancreatic cancer in a Chinese population. PMID: 26345895
  24. The TMPRSS2-ERG Gene Fusion Blocks XRCC4-Mediated Nonhomologous End-Joining Repair and Radiosensitizes Prostate Cancer Cells to PARP Inhibition. PMID: 26026052
  25. Point mutations in XRCC4 are associated with microcephaly, short stature, and genomic instability. PMID: 25839420
  26. Genetic susceptibility to schizophrenia was found in patients with genetic polymorphisms in intron 3 of the XRCC4 gene. PMID: 26112447
  27. Our results suggest that XRCC4 rs2075685 polymorphism plays an important role in the risk of pancreatic cancer in a Chinese population. PMID: 26045837
  28. Nonsense mutations in human XRCC4 have recently been associated with primordial dwarfism and, in our cases, with adult-onset neurological impairment, suggesting an important role for DNA repair in the brain. PMID: 25872942
  29. Polymorphisms of insertion/deletion at the intron 3 of the XRCC4 gene are associated with gastric cancer. PMID: 25527410
  30. Variants of the DNA damage repair gene XRCC4 increase the risk of esophageal cancer. PMID: 25612937
  31. No association was found between variants of XRCC4 rs2075685 and XRCC4 rs1805377 and the development of glioma. PMID: 25973104
  32. This study identified a novel pathogenic variant in XRCC4. This finding expands the spectrum of DNA damage repair syndromes to include XRCC4 deficiency, causing severe postnatal growth failure, microcephaly, gonadal failure, metabolic syndrome, and possibly tumor predisposition. PMID: 25742519
  33. Our data showed that Cd altered the phosphorylation of DNA-PKcs and reduced the expression of both XRCC4 and Ligase IV in irradiated cells. PMID: 26201248
  34. Our findings document the role of XRCC4 in non-BRCA1/2 breast cancer. PMID: 25360583
  35. The intron 3 VNTR polymorphism in the XRCC4 gene may be associated with the etiopathogenesis of RA as a marker of immune aging. PMID: 25494482
  36. The present results collectively indicated that Lys271, but not Lys210, of XRCC4 is required for the nuclear localization of XRCC4 and LIG4, and that the nuclear localizing ability is essential for the DSB repair function of XRCC4. PMID: 25934149
  37. The XRCC4 promoter -652G>T polymorphism is functional and may influence genetic susceptibility to prostate cancer. PMID: 25096509
  38. We present comprehensive genetic and cellular evidence that mutations in XRCC4 cause microcephalic primordial dwarfism. PMID: 25728776
  39. XRCC4 C-terminal point mutants, R325F and N326L, are functionally deficient in terms of cell survival after irradiation. PMID: 25597996
  40. There was longer survival among patients with non-invasive tumors associated with DNA repair X-ray repair cross-complementing protein 4 (XRCC4) heterozygous genotype compared with wild-type. PMID: 24666523
  41. Phosphorylation of XRCC4 in mitosis was not responsible for its failure to localize to mitotic chromosomes, and phosphorylation did not affect the interaction of XRCC4 with DNA ligase IV. PMID: 25165869
  42. Taken together, our results indicate that XRCC4 is required not only for the promotion of NHEJ during interphase but also for its M-phase-specific suppression of DSB repair. PMID: 25166505
  43. XRCC4 codon 247 polymorphism may be associated with DIA risk and prognosis among the Guangxi population. PMID: 24378850
  44. Results show that in cells deficient for Lig4, chromosomal translocation junctions had significantly longer deletions and more microhomologies. PMID: 25201414
  45. Characterization of the protein interaction domains that modulate the XRCC4/Ligase IV interaction. PMID: 23794378
  46. Single nucleotide polymorphisms in XRCC4 were associated with breast cancer risk. PMID: 24062231
  47. These results indicate for the first time that DNA ligase IV (LIG4) rs1805388 and X-ray Repair Cross Complementing-4 (XRCC4) rs1805377, alone or in combination, are associated with a risk of gliomas. PMID: 23663450
  48. The induced DNA damage by Methyl Methanesulfonate increases in Chronic Obstructive Pulmonary Disease patients with variant genotypes in OGG1 (Ser326Cys) showing impairment of DNA repair. PMID: 24053728
  49. XRCC4P may be a genetic modifier for the risk and outcome of hepatocellular carcinoma induced by aflatoxin B1 exposure. PMID: 23788213
  50. The chromatin binding of XRCC4 was dependent on the presence of LIG4. PMID: 23994631

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Database Links

HGNC: 12831

OMIM: 194363

KEGG: hsa:7518

STRING: 9606.ENSP00000342011

UniGene: Hs.567359

Involvement In Disease
Short stature, microcephaly, and endocrine dysfunction (SSMED)
Protein Families
XRCC4 family
Subcellular Location
Nucleus. Chromosome.; [Protein XRCC4, C-terminus]: Cytoplasm.
Tissue Specificity
Widely expressed.

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