DNA-repair protein complementing XP-G cells (ERCC5) (ERCC5)

DNA-repair protein complementing XP-G cells (ERCC5) is a magnesium-dependent endonuclease essential for the nucleotide excision repair (NER) pathway [1, 2]. It specifically catalyzes the 3' incision of damaged DNA strands to facilitate the removal of bulky lesions, such as those induced by ultraviolet radiation or platinum-based chemotherapy [1, 3]. Beyond its enzymatic role, ERCC5 serves as a structural scaffold for the assembly of the NER pre-incision complex and participates in transcription-coupled repair [3, 4]. Mutations in the ERCC5 gene are the primary cause of Xeroderma pigmentosum group G, a condition characterized by extreme sun sensitivity and a high risk of skin cancer, and can also lead to Cockayne syndrome [4]. In oncology, ERCC5 is a significant focus because its overexpression can confer resistance to platinum-based drugs like cisplatin, making it a potential target for sensitizing cancer cells to DNA-damaging agents [5]. Research is ongoing to develop small-molecule inhibitors of ERCC5 to overcome this resistance and improve treatment outcomes in various malignancies [5].

Other names

XPGXeroderma pigmentosum group G-complementing proteinExcision repair cross-complementing rodent repair deficiency complementation group 5

Inhibition of the 3' incision step in nucleotide excision repair to enhance the cytotoxicity of DNA-damaging agents [3, 5].