期刊
NATURE GENETICS
卷 44, 期 5, 页码 586-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2229
关键词
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资金
- Japan Science and Technology Agency (JST)
- Japanese Society for the Promotion of Science [22710056]
- Inamori Foundation
- Sagawa Foundation for Promotion of Cancer Research
- Mochida Memorial Funds for Medical and Pharmaceutical Research
- Daiichi-Sankyo Foundation of Life Science
- Takeda Science Foundation
- JST
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labour and Welfare
- Associazione Italiana per la Ricerca sul Cancro
- Medical Research Council (MRC)
- EC-RTN
- MRC [G0501450] Funding Source: UKRI
- Medical Research Council [G0801130B, G0501450] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [24681008, 22710056, 24659533, 23590355, 22791204, 22390189, 24790321] Funding Source: KAKEN
UV-sensitive syndrome ((UVS)-S-S) is a genodermatosis characterized by cutaneous photosensitivity without skin carcinoma(1-4). Despite mild clinical features, cells from individuals with (UVS)-S-S, like Cockayne syndrome cells, are very UV sensitive and are deficient in transcription-coupled nucleotide-excision repair (TC-NER)(2,4,5), which removes DNA damage in actively transcribed genes(6). Three of the seven known (UVS)-S-S cases carry mutations in the Cockayne syndrome genes ERCC8 or ERCC6 (also known as CSA and CSB, respectively)(7,8). The remaining four individuals with (UVS)-S-S, one of whom is described for the first time here, formed a separate (UVS)-S-S-A complementation group(1,9,10); however, the responsible gene was unknown. Using exome sequencing(11), we determine that mutations in the UVSSA gene (formerly known as KIAA1530) cause (UVS)-S-S-A. The UVSSA protein interacts with TC-NER machinery and stabilizes the ERCC6 complex; it also facilitates ubiquitination of RNA polymerase IIo stalled at DNA damage sites. Our findings provide mechanistic insights into the processing of stalled RNA polymerase and explain the different clinical features across these TC-NER-deficient disorders.
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