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

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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.

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References

    1. Somat Cell Mol Genet. 1987 May;13(3):279-84 - PubMed
    1. Genes Cells. 2011 Jan;16(1):101-14 - PubMed
    1. Cell Res. 2008 Jan;18(1):73-84 - PubMed
    1. J Mol Biol. 2008 Oct 3;382(2):266-74 - PubMed
    1. Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15410-5 - PubMed

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