Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair
| Autor: | Shunichi Yamashita, Alan R. Lehmann, Akira Kinoshita, Shinji Ono, Kaname Ohyama, Norisato Mitsutake, Michiko Matsuse, Katsuya Takenaka, Tomoo Ogi, Hiroyuki Mishima, Yuka Nakazawa, Kensaku Sasaki, Ritsuko Masuyama, Satoshi Tateishi, Yoshito Takahashi, Koh-ichiro Yoshiura, Takashi Kudo, Atsushi Utani, Miria Stefanini, Masayo Nomura, Kosei Ito, Tiziana Nardo, Mayuko Shimada, Hanoch Slor |
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| Rok vydání: | 2012 |
| Předmět: |
sequence analysis
DNA Repair Transcription Genetic ultraviolet stimulated scaffold protein a Cockayne syndrome suppressor of cytokine signaling chemistry.chemical_compound ultraviolet sensitive syndrome RNA polymerase Exome gene mutation Poly-ADP-Ribose Binding Proteins Genetics article unclassified drug priority journal RNA Polymerase II genodermatosis Transcription UV-sensitive syndrome Ultraviolet Rays DNA damage photosensitivity gene sequence Biology ubiquitination Genetic medicine Humans human Cockayne Syndrome Gene gene identification human cell DNA Helicases excision repair medicine.disease small interfering RNA Molecular biology DNA Repair Enzymes ERCC8 chemistry scaffold protein Mutation Carrier Proteins ERCC6 DNA Damage Transcription Factors |
| Zdroj: | Nature Genetics. 44:586-592 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.2229 |
| Popis: | UV-sensitive syndrome (UV SS) is a genodermatosis characterized by cutaneous photosensitivity without skin carcinoma. Despite mild clinical features, cells from individuals with UV SS, like Cockayne syndrome cells, are very UV sensitive and are deficient in transcription-coupled nucleotide-excision repair (TC-NER), which removes DNA damage in actively transcribed genes. Three of the seven known UV SS cases carry mutations in the Cockayne syndrome genes ERCC8 or ERCC6 (also known as CSA and CSB, respectively). The remaining four individuals with UV SS, one of whom is described for the first time here, formed a separate UV SS-A complementation group; however, the responsible gene was unknown. Using exome sequencing, we determine that mutations in the UVSSA gene (formerly known as KIAA1530) cause UV SS-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-NERg-deficient disorders. Nature Genetics, 44(5), pp.586-592; 2012 |
| Databáze: | OpenAIRE |
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