Excision repair cross-complementing rodent repair deficiency, complementation group 5 – Xeroderma pigmentosum, complementation group A interaction (ERCC5–XPA)

The ERCC5–XPA interaction is a pivotal protein-protein interface within the Nucleotide Excision Repair (NER) pathway, a major DNA repair mechanism that safeguards the genome against bulky adducts and UV-induced damage (1.1.4, 2.3.3). XPA (Xeroderma pigmentosum, complementation group A) acts as a central scaffold and damage-verification protein, recruiting other core NER factors to the lesion site (1.2.3, 3.4.4). Among these is ERCC5 (also known as XPG), a structure-specific endonuclease that performs the 3' incision of the damaged DNA strand (1.1.1, 2.2.1). This interaction is a significant therapeutic target in oncology, as inhibiting the NER pathway can sensitize cancer cells to DNA-damaging chemotherapeutic agents like cisplatin and carboplatin, thereby overcoming chemoresistance (1.2.1, 2.2.4). Drugs such as lurbinectedin exert their anti-tumor effects by binding to DNA and trapping NER proteins, including ERCC5, on the chromatin, which leads to lethal double-strand breaks (2.4.2). Mutations in the genes encoding these proteins are associated with severe genetic disorders such as Xeroderma Pigmentosum and Cockayne Syndrome, which are characterized by extreme photosensitivity and a high risk of skin cancer (1.1.3, 1.1.5).

Other names

XPG–XPA interactionERCC5–XPA complexNucleotide Excision Repair (NER) pre-incision complexXPG–XPA protein-protein interaction

Inhibition of nucleotide excision repair, DNA damage sensitization, DNA adduct trapping, and protein-protein interaction inhibition.