{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ERCC4 (also known as XPF) is a structure‐specific endonuclease that plays a key role in the maintenance of genome integrity by participating in several DNA repair pathways. In its canonical function, ERCC4 dimerizes with ERCC1 to form the ERCC1–XPF complex, which is required for nucleotide excision repair (NER) by incising at the junction between double‐stranded and single‐stranded DNA to remove bulky lesions caused by ultraviolet light and chemical carcinogens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, ERCC4–XPF functions in the repair of interstrand crosslinks (ICLs) as well as in certain double‐strand break repair pathways. When recruited to DNA damage sites by the scaffolding protein SLX4, the SLX1–SLX4–ERCC4 module contributes to processing replication forks and resolving recombination intermediates such as Holliday junctions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic mutations in ERCC4 can impair its endonuclease activity, selectively disrupting ICL repair while variably affecting NER, and have been implicated in rare human syndromes including variants of Fanconi anemia, xeroderma pigmentosum, and Cockayne syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, common polymorphisms in ERCC4 have been associated with modulated cancer risk and altered responses to DNA‐damaging chemotherapeutic agents such as cisplatin, with reduced ERCC4 expression contributing to increased drug sensitivity in certain tumor types."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, ERCC4 is a multifunctional nuclease whose activity is essential not only for the excision of bulky adducts in NER but also for processing complex DNA structures during ICL repair and recombination. Its interactions with partner proteins such as ERCC1 and SLX4 enable it to act in diverse repair contexts, and both loss‐of‐function mutations and common genetic variations in ERCC4 can have profound implications for genome stability and cancer susceptibility.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jennifer M Svendsen, Agata Smogorzewska, Mathew E Sowa, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.06.029"}], "href": "https://doi.org/10.1016/j.cell.2009.06.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19596236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19596236"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jian Ouyang, Elizabeth Garner, Alexander Hallet, et al. 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