title: Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6  in transcription-coupled DNA repair.
abstract: UV-sensitive syndrome (UV(S)S) is an autosomal recessive disorder characterized by photosensitivity and deficiency in transcription-coupled repair (TCR), a subpathway of nucleotide-excision repair that rapidly removes transcription-blocking DNA damage. Cockayne syndrome is a related disorder with defective TCR and consists of two complementation groups, Cockayne syndrome (CS)-A and CS-B, which are caused by mutations in ERCC8 (CSA) and ERCC6 (CSB), respectively. UV(S)S comprises three groups, UV(S)S/CS-A, UV(S)S/CS-B and UV(S)S-A, caused by mutations in ERCC8, ERCC6 and an unidentified gene, respectively. Here, we report the cloning of the gene mutated in UV(S)S-A by microcell-mediated chromosome transfer. The predicted human gene UVSSA (formerly known as KIAA1530)(7) corrects defective TCR in UV(S)S-A cells. We identify three nonsense and frameshift UVSSA mutations in individuals with UV(S)S-A, indicating that UVSSA is the causative gene for this syndrome. The UVSSA protein forms a complex with USP7 (ref. 8), stabilizes ERCC6 and restores the hypophosphorylated form of RNA polymerase II after UV irradiation.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Horibata
authors.forename: Masafumi
authors.initials: M
authors.lastname: Saijo
authors.forename: Chie
authors.initials: C
authors.lastname: Ishigami
authors.forename: Akiko
authors.initials: A
authors.lastname: Ukai
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kanno
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tahara
authors.forename: Edward G
authors.initials: EG
authors.lastname: Neilan
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Honma
authors.forename: Takehiko
authors.initials: T
authors.lastname: Nohmi
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D045643:DNA Repair Enzymes / Q000737:chemistry* / Q000235:genetics; D059472:Exome / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D055550:Protein Stability / Q000528:radiation effects*; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D002352:Carrier Proteins; C095472:ERCC8 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors; C573137:UVSSA protein, human; D012319:RNA Polymerase II; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes