DNA repair protein complementing XP-A cells (XPA)

DNA repair protein complementing XP-A cells (XPA) is the human gene product central to the nucleotide excision repair (NER) pathway, responsible for recognizing and verifying damaged DNA and acting as a scaffold for recruitment and organization of NER core factors[3][5]. XPA possesses a central DNA binding domain (residues 98–239) that binds to DNA junctions and interacts with other repair proteins, including replication protein A (RPA), ERCC1, and PCNA[2][1][5]. The protein itself lacks enzymatic activity, instead orchestrating the pre-incision complex in NER and participating in both global genome repair and transcription-coupled repair. Mutations in XPA can cause xeroderma pigmentosum, a disorder marked by extreme sensitivity to UV radiation and a greatly increased risk of skin cancer. XPA also has roles in other cellular processes beyond NER, such as involvement in the response to DNA replication stress and mitochondrial maintenance[1][2]. Severe mutations in XPA have been linked to neurodegeneration and accelerated aging[5].

Other names

XPAXPACXP1Xeroderma pigmentosum group A-complementing proteinDNA repair protein complementing XP-A cellsxeroderma pigmentosum group A-complementing proteinxeroderma pigmentosum, complementation group A

Drugs are not currently designed to directly target XPA itself. Instead, functional status of XPA affects cellular sensitivity to DNA-damaging agents: - In cells deficient in XPA, DNA damage accumulates, making them hypersensitive to DNA crosslinking agents (e.g., cisplatin)[2]. - Theoretically, an inhibitor of XPA would suppress repair of bulky DNA lesions, increasing cytotoxicity of DNA-damaging therapies.