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

被引：154

作者：

Zhang, Xue ^{[1
]}

Horibata, Katsuyoshi ^{[1
,2
]}

Saijo, Masafumi ^{[1
]}

Ishigami, Chie ^{[1
]}

Ukai, Akiko ^{[2
]}

Kanno, Shin-ichiro ^{[3
]}

Tahara, Hidetoshi ^{[4
]}

Neilan, Edward G. ^{[5
]}

Honma, Masamitsu ^{[2
]}

Nohmi, Takehiko ^{[2
]}

Yasui, Akira ^{[3
]}

Tanaka, Kiyoji ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Frontier Biosci, Osaka, Japan

[2] Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo, Japan

[3] Tohoku Univ, Div Dynam Proteome, Inst Dev Aging & Canc, Sendai, Miyagi 980, Japan

[4] Hiroshima Univ, Dept Cell & Mol Biol, Grad Sch Biomed Sci, Hiroshima, Japan

[5] Childrens Hosp, Div Genet, Ctr Life Sci Boston, Boston, MA 02115 USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 05期

关键词：

RNA-POLYMERASE-II; SYNDROME-B-PROTEIN; COCKAYNE-SYNDROME; XERODERMA-PIGMENTOSUM; NUCLEAR-MATRIX; SYNDROME CELLS; DAMAGE; CSA; TRANSLOCATION; DEGRADATION;

D O I：

10.1038/ng.2228

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

UV-sensitive syndrome ((UVS)-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(1). 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(2). (UVS)-S-S comprises three groups, (UVS)-S-S/CS-A, (UVS)-S-S/CS-B and (UVS)-S-S-A, caused by mutations in ERCC8, ERCC6 and an unidentified gene, respectively(3-6). Here, we report the cloning of the gene mutated in (UVS)-S-S-A by microcell-mediated chromosome transfer. The predicted human gene UVSSA (formerly known as KIAA1530)(7) corrects defective TCR in (UVS)-S-S-A cells. We identify three nonsense and frameshift UVSSA mutations in individuals with (UVS)-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.

引用

页码：593 / +

页数：6

共 32 条

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