9pcp
NER dual incision complex - NoG
Structural highlights
DiseaseERCC3_HUMAN IBIDS syndrome;Xeroderma pigmentosum complementation group B;PIBIDS syndrome;Xeroderma pigmentosum/Cockayne syndrome complex. Defects in ERCC3 are the cause of xeroderma pigmentosum complementation group B (XP-B) [MIM:610651; also known as xeroderma pigmentosum II (XP2) or XP group B (XPB) or xeroderma pigmentosum group B combined with Cockayne syndrome (XP-B/CS). Xeroderma pigmentosum is an autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Some XP-B patients present features of Cockayne syndrome, including dwarfism, sensorineural deafness, microcephaly, mental retardation, pigmentary retinopathy, ataxia, decreased nerve conduction velocities.[1] [2] Defects in ERCC3 are a cause of trichothiodystrophy photosensitive (TTDP) [MIM:601675. TTDP is an autosomal recessive disease characterized by sulfur-deficient brittle hair and nails, ichthyosis, mental retardation, impaired sexual development, abnormal facies and cutaneous photosensitivity correlated with a nucleotide excision repair (NER) defect. Neonates with trichothiodystrophy and ichthyosis are usually born with a collodion membrane. The severity of the ichthyosis after the membrane is shed is variable, ranging from a mild to severe lamellar ichthyotic phenotype. There are no reports of skin cancer associated with TTDP.[3] FunctionERCC3_HUMAN ATP-dependent 3'-5' DNA helicase, component of the core-TFIIH basal transcription factor, involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. Acts by opening DNA either around the RNA transcription start site or the DNA damage.[4] Publication Abstract from PubMedNucleotide excision repair (NER) removes bulky adducts from genomic DNA and prevents the ultraviolet light-sensitivity disease xeroderma pigmentosum, cancer and premature ageing(1). After initial lesion recognition by XPC in global genome repair or by stalled RNA polymerases in transcription-coupled repair, a lesion and surrounding DNA duplex are unwound by TFIIH, which includes the ATPases XPB and XPD, and additional NER factors XPA, XPF, XPG and RPA, to form a DNA bubble(2) comprising around 27 nucleotides. The double strand-single strand (ds-ss) junction-specific endonucleases XPF and XPG cleave DNA on the 5' and 3' sides of the lesion, respectively. Here we report the functional steps and atomic structures of the ATPase-driven and lesion-dependent DNA bubble formation and arrangement of the complete NER factors for dual incision. The unwinding of nearly 30 base pairs of DNA depends mainly on the double strand DNA translocase XPB and the duplex dividers XPA and XPF. XPD binds the lesion strand with XPF at the 5' ds-ss junction. XPF cuts the lesion strand only after XPG binds the 3' ds-ss junction. The ERCC1 subunit of XPF facilitates DNA strand separation and recruitment of RPA to the non-lesion strand. These findings provide insights on the causes of human diseases and potential targets for enhancing chemotherapeutic efficacy. Pre-incision structures reveal principles of DNA nucleotide excision repair.,Li ECL, Kim J, Brussee SJ, Sugasawa K, Luijsterburg MS, Yang W Nature. 2026 Feb 11. doi: 10.1038/s41586-026-10122-5. PMID:41673165[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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