DNA repair endonuclease ERCC5 (XPG) (ERCC5)

DNA repair endonuclease ERCC5, also known as XPG, is a structure-specific endonuclease that plays a pivotal role in the nucleotide excision repair (NER) pathway [1]. It specifically targets the "bubble" structure formed when DNA is damaged, recognizing the junction between single-stranded and double-stranded DNA created by the TFIIH complex [3]. ERCC5 is responsible for the 3' incision relative to the DNA lesion, which is a critical step for the removal of damaged nucleotides [1, 2]. Beyond its catalytic activity, it serves as a structural scaffold for other repair factors and is involved in transcription-coupled repair and the processing of oxidative DNA damage [3]. Mutations in the ERCC5 gene are the underlying cause of Xeroderma Pigmentosum group G and Cockayne Syndrome, conditions characterized by extreme sensitivity to ultraviolet light and progressive neurological decline [2]. In oncology, ERCC5 is considered a therapeutic target because its inhibition can enhance the efficacy of DNA-damaging chemotherapeutic agents, such as cisplatin, by preventing the repair of induced cross-links [4].

Other names

XPGXeroderma pigmentosum group G-complementing proteinUV24COFS3Excision repair cross-complementing group 5

Inhibition of the 3' endonuclease activity of ERCC5 to block the nucleotide excision repair (NER) pathway, thereby preventing the repair of DNA lesions and sensitizing cancer cells to DNA-damaging therapies [4].