ERCC5 – XPC–RAD23B complex (XPG-XPC-RAD23B)

The ERCC5 – XPC–RAD23B complex refers to a functional assembly of key proteins within the Nucleotide Excision Repair (NER) pathway, specifically the Global Genome NER (GG-NER) sub-pathway (NIH, 2025; Wikipedia, 2024). The XPC-RAD23B heterodimer (often associated with Centrin-2) serves as the primary sensor for helix-distorting DNA damage, such as UV-induced photoproducts and bulky chemical adducts (PNAS, 2015; NIH, 2012). Following damage recognition and recruitment of the TFIIH complex, ERCC5 (also known as XPG) is recruited to the site as a structure-specific endonuclease that performs the 3' incision of the damaged DNA strand (NIH, 2025; UniProt, 2024). This pathway is a critical mechanism for maintaining genomic stability and is a major determinant of cellular resistance to platinum-based chemotherapies like cisplatin (NIH, 2013; NIH, 2012). Consequently, these proteins are investigated as therapeutic targets to sensitize cancer cells to DNA-damaging agents and as biomarkers for predicting treatment response (NIH, 2026; NIH, 2013). Mutations in the genes encoding these proteins lead to severe genetic disorders, including Xeroderma pigmentosum and Cockayne syndrome, highlighting their critical role in maintaining genomic integrity (Wikipedia, 2024; PNAS, 2015).

Other names

XPG-XPC-RAD23B complexNucleotide excision repair (NER) machineryXeroderma pigmentosum group G and C proteinsGG-NER initiation and incision complex

Inhibition of the nucleotide excision repair (NER) pathway to enhance the efficacy of DNA-damaging chemotherapeutic agents.