Xeroderma pigmentosum group C protein (XPC)

Xeroderma pigmentosum group C protein (XPC) is a critical DNA damage recognition factor that initiates the Global Genomic Nucleotide Excision Repair (GG-NER) pathway [1, 3]. It functions as a primary sensor for helix-distorting DNA lesions, such as those induced by ultraviolet (UV) radiation or platinum-based chemotherapy [5, 10]. XPC operates within a heterotrimeric complex with RAD23B and centrin-2 to scan the genome and recruit the TFIIH complex to damaged sites [15, 27]. Mutations in the XPC gene lead to Xeroderma Pigmentosum group C, a rare autosomal recessive disorder characterized by extreme photosensitivity and a high predisposition to skin and internal malignancies [6, 16]. In clinical oncology, XPC expression and polymorphisms serve as important biomarkers for predicting patient response to DNA-damaging therapies [5, 24]. Furthermore, XPC is being investigated as a therapeutic target for sensitizing resistant tumors to chemotherapy by inhibiting its repair functions [20, 26].

Other names

XPCXP3XPCCp125RAD4DNA repair protein complementing XP-C cellsXeroderma pigmentosum group C-complementing proteinDNA damage recognition and repair factor

Restoration of functional XPC protein through gene therapy; inhibition of XPC-mediated DNA repair to sensitize cancer cells to platinum-based chemotherapy; bypassing XPC deficiency via delivery of exogenous DNA repair enzymes; and immune checkpoint blockade in tumors with high mutational burden resulting from XPC deficiency.