XRCC4

X-ray repair complementing defective repair in Chinese hamster cells 4
PDB rendering based on 1fu1.
Available structures PDB 1FU1, 1IK9, 3II6, 3MUD
Identifiers
Symbols	XRCC4;
External IDs	OMIM: 194363 MGI: 1333799 HomoloGene: 2555 GeneCards: XRCC4 Gene
Gene Ontology Molecular function • DNA binding • protein binding • protein C-terminus binding • ligase activity Cellular component • condensed chromosome • nucleus • nucleus • nucleoplasm • cytosol • DNA-dependent protein kinase-DNA ligase 4 complex • DNA ligase IV complex • nonhomologous end joining complex Biological process • in utero embryonic development • pro-B cell differentiation • DNA repair • double-strand break repair • double-strand break repair • double-strand break repair via nonhomologous end joining • double-strand break repair via nonhomologous end joining • double-strand break repair via nonhomologous end joining • double-strand break repair via nonhomologous end joining • central nervous system development • response to X-ray • response to gamma radiation • viral reproduction • provirus integration • initiation of viral infection • T cell differentiation in thymus • immunoglobulin V(D)J recombination • negative regulation of neuron apoptosis • isotype switching • positive regulation of fibroblast proliferation • positive regulation of neurogenesis • DNA ligation involved in DNA repair • positive regulation of ligase activity • cellular response to lithium ion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7518	108138
Ensembl	ENSG00000152422	ENSMUSG00000021615
UniProt	Q13426	Q924T3
RefSeq (mRNA)	NM_003401.3	NM_028012.4
RefSeq (protein)	NP_003392.1	NP_082288.1
Location (UCSC)	Chr 5: 82.37 – 82.65 Mb	Chr 13: 90.32 – 90.56 Mb
PubMed search	[1]	[2]

DNA repair protein XRCC4 is a protein that in humans is encoded by the XRCC4 gene.

Function

The protein encoded by this gene functions together with DNA ligase IV and the DNA-dependent protein kinase in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. The non-homologous end-joining pathway is required both for normal development and for suppression of tumors. This gene functionally complements XR-1 Chinese hamster ovary cell mutant, which is impaired in DNA double-strand breaks produced by ionizing radiation and restriction enzymes. This gene contains 8 exons, and alternative transcription initiation and alternative splicing generates several transcript variants.

Pathology

Mutations in XRCC4 are associated with embryonic lethality in mice specimens. This can be mitigated by crossing the XRCC4 knockouts with p53 mutants, suggesting that lethality is a result of p53 mediated apoptosis. In the hybrid XRCC4 deficient specimens, V(D)J recombination is severely impaired.

Interactions

XRCC4 has been shown to interact with LIG4 and XLF_Protein.

Further reading

• Lieber MR (1999). "The biochemistry and biological significance of nonhomologous DNA end joining: an essential repair process in multicellular eukaryotes.". Genes Cells 4 (2): 77–85. doi:10.1046/j.1365-2443.1999.00245.x. PMID 10320474. 
• Li Z, Otevrel T, Gao Y, et al. (1996). "The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination.". Cell 83 (7): 1079–89. doi:10.1016/0092-8674(95)90135-3. PMID 8548796. 
• Grawunder U, Wilm M, Wu X, et al. (1997). "Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells.". Nature 388 (6641): 492–5. doi:10.1038/41358. PMID 9242410. 
• Critchlow SE, Bowater RP, Jackson SP (1997). "Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV.". Curr. Biol. 7 (8): 588–98. doi:10.1016/S0960-9822(06)00258-2. PMID 9259561. 
• Mizuta R, Cheng HL, Gao Y, Alt FW (1998). "Molecular genetic characterization of XRCC4 function.". Int. Immunol. 9 (10): 1607–13. doi:10.1093/intimm/9.10.1607. PMID 9352367. 
• Leber R, Wise TW, Mizuta R, Meek K (1998). "The XRCC4 gene product is a target for and interacts with the DNA-dependent protein kinase.". J. Biol. Chem. 273 (3): 1794–801. doi:10.1074/jbc.273.3.1794. PMID 9430729. 
• Gao Y, Sun Y, Frank KM, et al. (1999). "A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis.". Cell 95 (7): 891–902. doi:10.1016/S0092-8674(00)81714-6. PMID 9875844. 
• Modesti M, Hesse JE, Gellert M (1999). "DNA binding of Xrcc4 protein is associated with V(D)J recombination but not with stimulation of DNA ligase IV activity.". EMBO J. 18 (7): 2008–18. doi:10.1093/emboj/18.7.2008. PMC 1171285. PMID 10202163. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171285. 
• Nick McElhinny SA, Snowden CM, McCarville J, Ramsden DA (2000). "Ku recruits the XRCC4-ligase IV complex to DNA ends.". Mol. Cell. Biol. 20 (9): 2996–3003. doi:10.1128/MCB.20.9.2996-3003.2000. PMC 85565. PMID 10757784. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85565. 
• Gao Y, Ferguson DO, Xie W, et al. (2000). "Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development.". Nature 404 (6780): 897–900. doi:10.1038/35009138. PMID 10786799. 
• Chen L, Trujillo K, Sung P, Tomkinson AE (2000). "Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase.". J. Biol. Chem. 275 (34): 26196–205. doi:10.1074/jbc.M000491200. PMID 10854421. 
• Lee KJ, Huang J, Takeda Y, Dynan WS (2000). "DNA ligase IV and XRCC4 form a stable mixed tetramer that functions synergistically with other repair factors in a cell-free end-joining system.". J. Biol. Chem. 275 (44): 34787–96. doi:10.1074/jbc.M004011200. PMID 10945980. 
• Ford BN, Ruttan CC, Kyle VL, et al. (2000). "Identification of single nucleotide polymorphisms in human DNA repair genes.". Carcinogenesis 21 (11): 1977–81. doi:10.1093/carcin/21.11.1977. PMID 11062157. 
• Sibanda BL, Critchlow SE, Begun J, et al. (2002). "Crystal structure of an Xrcc4-DNA ligase IV complex.". Nat. Struct. Biol. 8 (12): 1015–9. doi:10.1038/nsb725. PMID 11702069. 
• Lee KJ, Dong X, Wang J, et al. (2002). "Identification of human autoantibodies to the DNA ligase IV/XRCC4 complex and mapping of an autoimmune epitope to a potential regulatory region.". J. Immunol. 169 (6): 3413–21. PMID 12218164. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Hsu HL, Yannone SM, Chen DJ (2003). "Defining interactions between DNA-PK and ligase IV/XRCC4.". DNA Repair (Amst.) 1 (3): 225–35. doi:10.1016/S1568-7864(01)00018-0. PMID 12509254. 

External links

• MeSH XRCC4+protein,+human
• FactorBook XRCC4