{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nXRCC5, which encodes the Ku80 subunit of the Ku heterodimer, is central to the non‐homologous end joining (NHEJ) pathway that repairs DNA double‐strand breaks. As evidenced in several studies, Ku80 rapidly binds to DNA breaks (in concert with Ku70) to form a dynamic platform that recruits and organizes downstream factors—including DNA‐PKcs, XRCC4/ligase IV, XLF, and APLF—ensuring proper end‐tethering and ligation. Structural and biochemical analyses have revealed that Ku80 not only mediates the initial detection of breaks but also undergoes conformational changes, interacts with various repair proteins, and is subject to regulated post‐translational modifications (e.g., dephosphorylation and ubiquitylation) that fine‐tune its dissociation from DNA once repair is completed."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in DSB repair, XRCC5/Ku80 exhibits additional functions critical for genome maintenance. It contributes to telomere homeostasis by interacting directly with telomerase components and binding specific RNA regions, and it even partakes in transcriptional regulation—for instance, through associations with transcription elongation complexes or as a coactivator with hormone receptors. Moreover, Ku80 influences DNA replication dynamics and cell‐cycle progression by assisting in the assembly of replication factors, thereby linking its repair activity to broader cellular processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinical and genetic studies underscore the significance of XRCC5 in preserving genomic integrity, with polymorphic variants and altered expression levels associated with susceptibility to various cancers—including lung, breast, glioma, head and neck, hepatocellular, and oral cancers—and with differences in radiotherapy response. These findings, together with evidence that XRCC5/Ku80 activity is modulated by stress- and cell cycle–dependent signals (as well as redox and post‐translational regulatory events), highlight its multifaceted role not only in the repair of DNA lesions but also in the maintenance of cellular homeostasis and genome stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xianming Mo, William S Dynan "}, {"type": "b", "children": [{"type": "t", "text": "Subnuclear localization of Ku protein: functional association with RNA polymerase II elongation sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.22.8088-8099.2002"}], "href": "https://doi.org/10.1128/MCB.22.22.8088-8099.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12391174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12391174"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Manabu Koike "}, {"type": "b", "children": [{"type": "t", "text": "Dimerization, translocation and localization of Ku70 and Ku80 proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Radiat Res (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1269/jrr.43.223"}], "href": "https://doi.org/10.1269/jrr.43.223"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12518983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12518983"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Patrick Calsou, Christine Delteil, Philippe Frit, et al. 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