DNA repair protein complementation group A (XPA) (XPA)

DNA repair protein complementation group A (XPA) is a critical scaffold protein essential for the nucleotide excision repair (NER) pathway, which identifies and removes bulky DNA lesions caused by UV radiation and chemical mutagens (UniProt P23025). XPA functions by binding to damaged DNA and coordinating the assembly of other NER factors, such as Replication Protein A (RPA) and Transcription Factor IIH (TFIIH), at the site of the lesion (NCBI Gene ID 7507). Mutations in the XPA gene lead to Xeroderma pigmentosum group A, a severe genetic condition characterized by extreme sun sensitivity and a high risk of skin cancer (PubMed 25532593). In oncology, XPA is a significant therapeutic target because its overexpression often contributes to resistance against platinum-based chemotherapies, which rely on inducing DNA damage that NER would otherwise repair (PubMed 31430441). Current drug development efforts focus on small molecule inhibitors that disrupt XPA's interaction with DNA or its protein partners to enhance the efficacy of DNA-damaging treatments in resistant tumors (PubMed 23175493).

Other names

Xeroderma pigmentosum group A proteinXPACXeroderma pigmentosum, complementation group ADNA repair protein complementation group A

Inhibition of the XPA-DNA binding domain or disruption of the XPA-RPA70 interaction to prevent the assembly of the nucleotide excision repair (NER) complex, thereby sensitizing cancer cells to DNA-damaging agents.