Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair

Xue Zhang, Katsuyoshi Horibata, Masafumi Saijo, Chie Ishigami, Akiko Ukai, Shin Ichiro Kanno, Hidetoshi Tahara, Edward G. Neilan, Masamitsu Honma, Takehiko Nohmi, Akira Yasui, Kiyoji Tanaka

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)

Abstract

UV-sensitive syndrome (UV SS) 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 SS comprises three groups, UV SS/CS-A, UV SS/CS-B and UV SS-A, caused by mutations in ERCC8, ERCC6 and an unidentified gene, respectively. Here, we report the cloning of the gene mutated in UV SS-A by microcell-mediated chromosome transfer. The predicted human gene UVSSA (formerly known as KIAA1530) corrects defective TCR in UV SS-A cells. We identify three nonsense and frameshift UVSSA mutations in individuals with UV SS-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.

Original languageEnglish
Pages (from-to)593-597
Number of pages5
JournalNature Genetics
Volume44
Issue number5
DOIs
Publication statusPublished - 2012 May

ASJC Scopus subject areas

  • Genetics

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