{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:32:32Z","timestamp":1790688752810,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","funder":[{"name":"Intramural Research Program"},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bench-to-Bedside Program"},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Luke O\u2019Brien Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cockayne Syndrome (CS) is a rare neurodegenerative disease characterized by short stature, accelerated aging and short lifespan. Mutations in two human genes, ERCC8\/CSA and ERCC6\/CSB, are causative for CS and their protein products, CSA and CSB, while structurally unrelated, play roles in DNA repair and other aspects of DNA metabolism in human cells. Many clinical and molecular features of CS remain poorly understood, and it was observed that CSA and CSB regulate transcription of ribosomal DNA (rDNA) genes and ribosome biogenesis. Here, we investigate the dysregulation of rRNA synthesis in CS. We report that Nucleolin (Ncl), a nucleolar protein that regulates rRNA synthesis and ribosome biogenesis, interacts with CSA and CSB. In addition, CSA induces ubiquitination of Ncl, enhances binding of CSB to Ncl, and CSA and CSB both stimulate the binding of Ncl to rDNA and subsequent rRNA synthesis. CSB and CSA also increase RNA Polymerase I loading to the coding region of the rDNA and this is Ncl dependent. These findings suggest that CSA and CSB are positive regulators of rRNA synthesis via Ncl regulation. Most CS patients carry mutations in CSA and CSB and present with similar clinical features, thus our findings provide novel insights into disease mechanism.<\/jats:p>","DOI":"10.1093\/nar\/gkz1242","type":"journal-article","created":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T15:10:17Z","timestamp":1577805017000},"page":"2473-2485","source":"Crossref","is-referenced-by-count":44,"title":["Cockayne syndrome group A and B proteins function in rRNA transcription through nucleolin regulation"],"prefix":"10.1093","volume":"48","author":[{"given":"Mustafa N","family":"Okur","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hyuk","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasif","family":"Osmani","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risako","family":"Kimura","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler G","family":"Demarest","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L","family":"Croteau","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4823-6429","authenticated-orcid":false,"given":"Vilhelm A","family":"Bohr","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA"},{"name":"Danish Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"2020030203101930200_B1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.arr.2016.08.002","article-title":"Cockayne syndrome: Clinical features, model systems and pathways","volume":"33","author":"Karikkineth","year":"2017","journal-title":"Ageing Res. 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Ageing Dev."},{"key":"2020030203101930200_B3","doi-asserted-by":"crossref","first-page":"5955","DOI":"10.1093\/emboj\/16.19.5955","article-title":"The Cockayne syndrome B protein, involved in transcription-coupled DNA repair, resides in an RNA polymerase II-containing complex","volume":"16","author":"van\u00a0Gool","year":"1997","journal-title":"EMBO J."},{"key":"2020030203101930200_B4","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/0092-8674(92)90390-X","article-title":"ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes","volume":"71","author":"Troelstra","year":"1992","journal-title":"Cell"},{"key":"2020030203101930200_B5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/cr.2008.6","article-title":"Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects","volume":"18","author":"Fousteri","year":"2008","journal-title":"Cell Res."},{"key":"2020030203101930200_B6","doi-asserted-by":"crossref","first-page":"5246","DOI":"10.1093\/nar\/gkw216","article-title":"A ubiquitylation site in Cockayne syndrome B required for repair of oxidative DNA damage, but not for transcription-coupled nucleotide excision repair","volume":"44","author":"Ranes","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2020030203101930200_B7","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.molcel.2010.04.017","article-title":"A ubiquitin-binding domain in Cockayne syndrome B required for transcription-coupled nucleotide excision repair","volume":"38","author":"Anindya","year":"2010","journal-title":"Mol. Cell"},{"key":"2020030203101930200_B8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jmb.2015.11.020","article-title":"Elements that regulate the dna damage response of proteins defective in cockayne syndrome","volume":"428","author":"Iyama","year":"2016","journal-title":"J. Mol. Biol."},{"key":"2020030203101930200_B9","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.4161\/cc.29018","article-title":"Cockayne syndrome protein A is a transcription factor of RNA polymerase I and stimulates ribosomal biogenesis and growth","volume":"13","author":"Koch","year":"2014","journal-title":"Cell Cycle"},{"key":"2020030203101930200_B10","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/0955-0674(95)80085-9","article-title":"The nucleolus: an organelle formed by the act of building a ribosome","volume":"7","author":"Melese","year":"1995","journal-title":"Curr. Opin. Cell Biol."},{"key":"2020030203101930200_B11","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1242\/jcs.111948","article-title":"Eukaryotic ribosome biogenesis at a glance","volume":"126","author":"Thomson","year":"2013","journal-title":"J. Cell Sci."},{"key":"2020030203101930200_B12","doi-asserted-by":"crossref","first-page":"402","DOI":"10.4161\/nucl.32235","article-title":"Nucleolar stress with and without p53","volume":"5","author":"James","year":"2014","journal-title":"Nucleus"},{"key":"2020030203101930200_B13","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18071411","article-title":"The Nucleolus: In Genome Maintenance and Repair","volume":"18","author":"Tsekrekou","year":"2017","journal-title":"Int. J. Mol. 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