Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair - PubMed (original) (raw)
Katsuyoshi Horibata, Masafumi Saijo, Chie Ishigami, Akiko Ukai, Shin-ichiro Kanno, Hidetoshi Tahara, Edward G Neilan, Masamitsu Honma, Takehiko Nohmi, Akira Yasui, Kiyoji Tanaka
Affiliations
- PMID: 22466612
- DOI: 10.1038/ng.2228
Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair
Xue Zhang et al. Nat Genet. 2012 May.
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.
Comment in
- Photosensitivity syndrome brings to light a new transcription-coupled DNA repair cofactor.
Cleaver JE. Cleaver JE. Nat Genet. 2012 Apr 26;44(5):477-8. doi: 10.1038/ng.2255. Nat Genet. 2012. PMID: 22538718
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