{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nXRCC4 is a key nonenzymatic scaffold protein that plays an essential role in the repair of DNA double‐strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. Structural and biochemical studies have revealed that XRCC4 forms a stable complex with DNA ligase IV—where a single ligase IV molecule associates asymmetrically with an XRCC4 dimer—to promote precise ligation of broken DNA ends, even across small gaps or incompatible overhangs. In addition, XRCC4 works cooperatively with the Ku70/80 heterodimer and interacts directly with other NHEJ factors, thereby contributing to the reversible assembly of core repair components at DSBs. This essential role is further underscored by its ability to serve as a flexible tether between Ku70/80 and ligase IV, as well as by its involvement in gap filling processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its basic scaffolding function, XRCC4 is dynamically regulated and forms higher-order assemblies that are critical for efficient DSB repair. Studies using single-molecule imaging and optical tweezers have shown that XRCC4, in complex with XRCC4-like factor (XLF), can bridge and align DNA ends by forming mobile, filamentous structures that act as a sleeve encasing the DNA to facilitate ligation. Moreover, post-translational modifications such as phosphorylation and SUMOylation—as well as regulation by ubiquitin ligases—modulate XRCC4’s interaction with DNA ligase IV and other repair enzymes such as polynucleotide kinase/phosphatase, thereby fine-tuning repair kinetics and fidelity during cellular responses to DNA damage including V(D)J recombination and class switch recombination."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "22"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctionally, XRCC4’s central role in NHEJ contributes not only to the rapid and accurate repair of DSBs but also to the maintenance of genomic stability during development. Its proper function is critical for preventing chromosomal aberrations that can lead to diseases ranging from immunodeficiency and cancer predisposition to developmental disorders such as microcephalic primordial dwarfism. Recent cryo-electron microscopy studies and in vitro repair assays further emphasize that XRCC4–XLF assemblies generate a protective and flexible scaffold that orchestrates the spatial proximity of broken DNA ends for repair, establishing XRCC4 as a linchpin of the cellular DSB repair machinery."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pierre-Olivier Mari, Bogdan I Florea, Stephan P Persengiev, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of an Xrcc4-DNA ligase IV complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Biol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsb725"}], "href": "https://doi.org/10.1038/nsb725"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11702069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11702069"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jae Wan Lee, Luis Blanco, Tong Zhou, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "DNA-dependent protein kinase and XRCC4-DNA ligase IV mobilization in the cell in response to DNA double strand breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M410746200"}], "href": "https://doi.org/10.1074/jbc.M410746200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15520013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15520013"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sara N Andres, Alexandra Vergnes, Dejan Ristic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A human XRCC4-XLF complex bridges DNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gks022"}], "href": "https://doi.org/10.1093/nar/gks022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22287571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22287571"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Pauline Soulas-Sprauel, Gwenaël Le Guyader, Paola Rivera-Munoz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role for DNA repair factor XRCC4 in immunoglobulin class switch recombination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20070255"}], "href": "https://doi.org/10.1084/jem.20070255"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17606631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17606631"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sara N Andres, Mauro Modesti, Chun J Tsai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of human XLF: a twist in nonhomologous DNA end-joining."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.10.024"}], "href": "https://doi.org/10.1016/j.molcel.2007.10.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18158905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18158905"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Peï-Yu Wu, Philippe Frit, SriLakshmi Meesala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional interaction between the human DNA repair proteins DNA ligase IV and XRCC4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01895-08"}], "href": "https://doi.org/10.1128/MCB.01895-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19332554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19332554"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Virginie Ropars, Pascal Drevet, Pierre Legrand, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Interaction of the Ku heterodimer with the DNA ligase IV/Xrcc4 complex and its regulation by DNA-PK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Repair (Amst) (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dnarep.2006.12.007"}], "href": "https://doi.org/10.1016/j.dnarep.2006.12.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17241822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17241822"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Isabelle Callebaut, Laurent Malivert, Alain Fischer, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0022-2836(02)01328-1"}], "href": "https://doi.org/10.1016/s0022-2836(02"}, {"type": "t", "text": "01328-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12547193"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12547193"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Haihui Lu, Ulrich Pannicke, Klaus Schwarz, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Dual modes of interaction between XRCC4 and polynucleotide kinase/phosphatase: implications for nonhomologous end joining."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.058719"}], "href": "https://doi.org/10.1074/jbc.M109.058719"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20852255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20852255"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Jennie E Murray, Mirjam van der Burg, Hanna IJspeert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the NHEJ component XRCC4 cause primordial dwarfism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2015.01.013"}], "href": "https://doi.org/10.1016/j.ajhg.2015.01.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25728776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25728776"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Qian Wu, Takashi Ochi, Dijana Matak-Vinkovic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Non-homologous end-joining partners in a helical dance: structural studies of XLF-XRCC4 interactions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST0391387"}], "href": "https://doi.org/10.1042/BST0391387"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21936820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21936820"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Amanda K Chaplin, Steven W Hardwick, Antonia Kefala Stavridi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cryo-EM of NHEJ supercomplexes provides insights into DNA repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2021.07.005"}], "href": "https://doi.org/10.1016/j.molcel.2021.07.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34352203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34352203"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Brandi L Mahaney, Michal Hammel, Katheryn Meek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Cell Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1139/bcb-2012-0058"}], "href": "https://doi.org/10.1139/bcb-2012-0058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23442139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23442139"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Bret R Adams, Amy J Hawkins, Lawrence F Povirk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATM-independent, high-fidelity nonhomologous end joining predominates in human embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.100197"}], "href": "https://doi.org/10.18632/aging.100197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20844317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20844317"}]}]}]}