{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:14:40Z","timestamp":1791159280529,"version":"4.1.0"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,1,15]]},"abstract":"<jats:p>\n                    Specific mutations in the\n                    <jats:italic>XPD<\/jats:italic>\n                    subunit of transcription factor IIH result in combined xeroderma pigmentosum (XP)\/Cockayne syndrome (CS), a severe DNA repair disorder characterized at the cellular level by a transcriptional arrest following UV irradiation. This transcriptional arrest has always been thought to be the result of faulty transcription-coupled repair. In the present study, we showed that, following UV irradiation, XP-D\/CS cells displayed a gross transcriptional dysregulation compared with \u201cpure\u201d XP-D cells or WT cells. Furthermore, global RNA-sequencing analysis showed that XP-D\/CS cells repressed the majority of genes after UV, whereas pure XP-D cells did not. By using housekeeping genes as a model, we demonstrated that XP-D\/CS cells were unable to reassemble these gene promoters and thus to restart transcription after UV irradiation. Furthermore, we found that the repression of these promoters in XP-D\/CS cells was not a simple consequence of deficient repair but rather an active heterochromatinization process mediated by the histone deacetylase Sirt1. Indeed, RNA-sequencing analysis showed that inhibition of and\/or silencing of Sirt1 changed the chromatin environment at these promoters and restored the transcription of a large portion of the repressed genes in XP-D\/CS cells after UV irradiation. Our work demonstrates that a significant part of the transcriptional arrest displayed by XP-D\/CS cells arises as a result of an active repression process and not simply as a result of a DNA repair deficiency. This dysregulation of Sirt1 function that results in transcriptional repression may be the cause of various severe clinical features in patients with XP-D\/CS that cannot be explained by a DNA repair defect.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1213076110","type":"journal-article","created":{"date-parts":[[2012,12,24]],"date-time":"2012-12-24T23:14:38Z","timestamp":1356390878000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":28,"title":["Sirt1 suppresses RNA synthesis after UV irradiation in combined xeroderma pigmentosum group D\/Cockayne syndrome (XP-D\/CS) cells"],"prefix":"10.1073","volume":"110","author":[{"given":"Renier","family":"V\u00e9lez-Cruz","sequence":"first","affiliation":[{"name":"Department of Functional Genomics and Cancer, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 de Strasbourg, 67404 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton S.","family":"Zadorin","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics and Cancer, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 de Strasbourg, 67404 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Coin","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics and Cancer, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 de Strasbourg, 67404 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Egly","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics and Cancer, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 de Strasbourg, 67404 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,12,24]]},"reference":[{"key":"e_1_1_2_17_9_1_2","first-page":"1473","article-title":"Failure of RNA synthesis to recover after UV irradiation: An early defect in cells from individuals with Cockayne\u2019s syndrome and xeroderma pigmentosum","volume":"42","author":"Mayne LV","year":"1982","unstructured":"LV Mayne, AR Lehmann, Failure of RNA synthesis to recover after UV irradiation: An early defect in cells from individuals with Cockayne\u2019s syndrome and xeroderma pigmentosum. 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