DNA excision repair protein ERCC-5 (ERCC5)

DNA excision repair protein ERCC-5 (commonly known as XPG, encoded by ERCC5) is a single-strand specific structure-specific DNA endonuclease central to nucleotide excision repair (NER), base excision repair (BER), and transcription-coupled repair (TCR)[1][2][3][5]. XPG makes a critical 3' incision at sites of DNA damage, particularly following UV-induced lesions, and also acts as a scaffold coordinating the assembly of multi-protein DNA repair complexes[1][2][3]. Loss-of-function mutations in ERCC5 cause rare autosomal recessive syndromes including xeroderma pigmentosum group G (XP-G, highly UV-sensitive, cancer-prone), Cockayne syndrome (developmental and neurodegenerative, without cancer predisposition), and cerebro-oculo-facio-skeletal syndrome (COFS3)[1][2][4]. In addition to its endonuclease activity, XPG binds and distorts DNA repair 'bubble' intermediates, facilitating the correct repair of lesions and interfacing with key genes involved in homologous recombination and replication fork protection (e.g., BRCA1/2, RAD51)[3]. It is part of the FEN nuclease superfamily and mutations manifest through loss of either its catalytic function, structural integrity, or interaction capacity, leading to genomic instability, disease, and increased sensitivity to DNA-damaging conditions[1][2][3][5].

Other names

DNA repair protein complementing XP-G cellsERCM2XPGXPGCexcision repair cross-complementation group 5xeroderma pigmentosum group G-complementing proteinCockayne syndrome (COFS3)excision repair cross-complementing rodent repair deficiency, complementation group 5DNA excision repair protein ERCC-5

Cleavage of damaged DNA 3' to lesion during excision repair; scaffolding for DNA repair protein complexes; DNA bubble binding and destabilization; stimulation of other repair enzymes (e.g., NTHL1 in BER); interaction with transcription and replication machinery