TY - JOUR
T1 - Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair
AU - Zhang, Xue
AU - Horibata, Katsuyoshi
AU - Saijo, Masafumi
AU - Ishigami, Chie
AU - Ukai, Akiko
AU - Kanno, Shin Ichiro
AU - Tahara, Hidetoshi
AU - Neilan, Edward G.
AU - Honma, Masamitsu
AU - Nohmi, Takehiko
AU - Yasui, Akira
AU - Tanaka, Kiyoji
N1 - Funding Information:
We thank Y. Iwamoto and I. Kuraoka for their help in DNA sequencing and microcell-mediated chromosome transfer and M. Hoshi for her help in establishing Flp-In cells and performing immunoprecipitation. We also thank M. Yamaizumi (Kumamoto University Medical School) and N.G. Jaspers (Erasmus Medical Centre) for providing Kps3 cells and TA-24 cells, respectively. We thank G. Spivak for critical reading of the manuscript. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and by Health and Labor Sciences Research Grants for Research on Intractable Diseases (to K.T.). Part of this work was carried out under the Cooperative Research Project Program of the Institute of Development, Aging and Cancer (IDAC) at Tohoku University.
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
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U2 - 10.1038/ng.2228
DO - 10.1038/ng.2228
M3 - Article
C2 - 22466612
AN - SCOPUS:84860336243
VL - 44
SP - 593
EP - 597
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 5
ER -