{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nXPA is a core factor in nucleotide excision repair (NER) that functions as a central organizer and damage verifier. It binds damaged DNA in a largely nonspecific manner but, through partnerships with proteins such as replication protein A (RPA), it helps stabilize the distorted DNA structure and coordinate subsequent incision events. Studies using biochemical and in vivo fluorescence techniques have shown that XPA is rapidly mobile in the nucleoplasm yet becomes transiently immobilized at sites of damage through an XPC‐dependent mechanism. Furthermore, its expression is subject to circadian oscillations and regulated posttranslationally (for example, via ATR‐mediated phosphorylation and SIRT1‐driven deacetylation), alterations that modulate its stability and interactions during repair."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic polymorphisms in the XPA gene have been implicated in modulating individual NER capacity and, consequently, cancer risk and treatment response. Several investigations have assessed variants such as the –4G>A and A23G in diverse patient populations. Reduced or altered XPA levels—as observed in testicular tumor cell lines—correlate with increased sensitivity to cisplatin‐based chemotherapy, while specific XPA genotypes have been linked to differences in polycyclic aromatic hydrocarbon–DNA adduct levels and lung cancer susceptibility. Such studies underscore the clinical relevance of inherited variation in XPA for both carcinogenesis and prognosis across several cancer types."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn terms of repair‐complex assembly and lesion verification, XPA is not the primary lesion recognizer but is instead recruited to sites of damage after initial recognition by factors such as XPC. Live‐cell imaging has revealed that a pool of free, rapidly diffusing XPA is successively incorporated into repair complexes in a highly dynamic, time‐dependent manner. This sequential recruitment, together with its interactions with other NER proteins, is critical for the dual incision process that ultimately excises bulky lesions. Such studies further delineate the mechanistic role of XPA in verifying and stabilizing damaged DNA intermediates during repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Karen M Vasquez, Jesper Christensen, Lei Li, et al. 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