| Title: |
UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair |
| Authors: |
Schwertman, Petra; Lagarou, Anna; Dekkers, Dick; Raams, Anja; Hoek, Rianne; Laffeber, Charlie; Hoeijmakers, Jan; Demmers, Jeroen; Fousteri, M; Vermeulen, Wim; Marteijn, Jurgen |
| Source: |
Schwertman, P, Lagarou, A, Dekkers, D, Raams, A, Hoek, R, Laffeber, C, Hoeijmakers, J, Demmers, J, Fousteri, M, Vermeulen, W & Marteijn, J 2012, 'UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair', Nature Genetics, vol. 44, no. 5, pp. 598-602. https://doi.org/10.1038/ng.2230 |
| Publication Year: |
2012 |
| Subject Terms: |
/dk/atira/pure/keywords/researchprograms/AFL001000/EMCMGC011203; name=EMC MGC-01-12-03; /dk/atira/pure/keywords/researchprograms/AFL001000/EMCMGC022101; name=EMC MGC-02-21-01 |
| Description: |
Transcription-coupled nucleotide-excision repair (TC-NER) is a subpathway of NER that efficiently removes the highly toxic RNA polymerase II blocking lesions in DNA. Defective TC-NER gives rise to the human disorders Cockayne syndrome and UV-sensitive syndrome (UVSS)(1). NER initiating factors are known to be regulated by ubiquitination(2). Using a SILAC-based proteomic approach, we identified UVSSA (formerly known as KIAA1530) as part of a UV-induced ubiquitinated protein complex. Knockdown of UVSSA resulted in TC-NER deficiency. UVSSA was found to be the causative gene for UVSS, an unresolved NER deficiency disorder(3). The UVSSA protein interacts with elongating RNA polymerase II, localizes specifically to UV-induced lesions, resides in chromatin-associated TC-NER complexes and is implicated in stabilizing the TC-NER master organizing protein ERCC6 (also known as CSB) by delivering the deubiquitinating enzyme USP7 to TC-NER complexes. Together, these findings indicate that UVSSA-USP7-mediated stabilization of ERCC6 represents a critical regulatory mechanism of TC-NER in restoring gene expression. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| ISSN: |
1061-4036; 1546-1718 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/22466611; info:eu-repo/semantics/altIdentifier/pissn/1061-4036; info:eu-repo/semantics/altIdentifier/eissn/1546-1718 |
| DOI: |
10.1038/ng.2230 |
| Availability: |
https://pure.eur.nl/en/publications/d1b6d9d3-495b-4755-b90b-383ef3ab918f; https://doi.org/10.1038/ng.2230; https://hdl.handle.net/1765/59964 |
| Rights: |
info:eu-repo/semantics/closedAccess |
| Accession Number: |
edsbas.3D751D06 |
| Database: |
BASE |