{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPAXX (PAralog of XRCC4 and XLF) is a recently identified member of the XRCC4 superfamily that plays an important role in the repair of DNA double‐strand breaks (DSBs) via the classical nonhomologous end joining (NHEJ) pathway. Its structure closely resembles that of XRCC4 and XLF, and it is rapidly recruited to sites of DNA damage through direct interaction with the Ku heterodimer. Loss‐of‐function studies using RNA interference and CRISPR-Cas9 have demonstrated that PAXX is required for efficient DSB repair and cell survival following exposure to DSB-inducing agents."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemical and structural analyses have revealed that PAXX contains a conserved C-terminal Ku-binding motif that facilitates its incorporation into larger repair complexes. By forming stable assemblies with Ku—including simultaneous binding with XLF—and bridging partner interactions, PAXX enhances Ku-dependent DNA ligation and supports the recruitment of downstream repair factors. In addition, PAXX has been shown to interact with DNA polymerases such as polymerase λ and polymerase β, thereby stimulating polymerase activity during end processing and gap filling in NHEJ as well as contributing to base excision repair pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic analyses underscore the accessory yet critical function of PAXX in DSB repair. Although cells deficient for PAXX sometimes exhibit only modest repair defects—likely owing to functional redundancy with factors such as XLF—combined loss of PAXX with other NHEJ components (for instance, XLF or DNA-PKcs) leads to synthetic lethality in animal models, highlighting overlapping roles in stabilizing DNA repair complexes. Moreover, recent studies indicate that while loss of core factors like XRCC4 prominently impairs repair, PAXX’s contribution becomes increasingly essential under conditions that challenge the repair machinery, with potential implications in contexts such as radioresistance and chemotherapeutic response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takashi Ochi, Andrew N Blackford, Julia Coates, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1261971"}], "href": "https://doi.org/10.1126/science.1261971"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25574025"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25574025"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mengtan Xing, Mingrui Yang, Wei Huo, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PAXX Participates in Base Excision Repair via Interacting with Pol β and Contributes to TMZ Resistance in Glioma Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-018-1157-4"}], "href": "https://doi.org/10.1007/s12031-018-1157-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30238427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30238427"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Andrew Craxton, Deeksha Munnur, Rebekah Jukes-Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAXX and its paralogs synergistically direct DNA polymerase λ activity in DNA repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-06127-y"}], "href": "https://doi.org/10.1038/s41467-018-06127-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30250067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30250067"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Murielle Seif-El-Dahan, Antonia Kefala-Stavridi, Philippe Frit, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAXX binding to the NHEJ machinery explains functional redundancy with XLF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Adv (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciadv.adg2834"}], "href": "https://doi.org/10.1126/sciadv.adg2834"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37256950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37256950"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Satish K Tadi, Carine Tellier-Lebègue, Clément Nemoz, et al. 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