{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:21:42Z","timestamp":1789428102574,"version":"build-2803163510"},"reference-count":107,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2019\/35\/B\/NZ5\/00695"],"award-info":[{"award-number":["2019\/35\/B\/NZ5\/00695"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre of Postgraduate Medical Education","award":["501-1-025-01-20"],"award-info":[{"award-number":["501-1-025-01-20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The nucleoli are membrane-less nuclear substructures that govern ribosome biogenesis and participate in multiple other cellular processes such as cell cycle progression, stress sensing, and DNA damage response. The proper functioning of these organelles is ensured by specific proteins that maintain nucleolar structure and mediate key nucleolar activities. Among all nucleolar proteins, treacle encoded by TCOF1 gene emerges as one of the most crucial regulators of cellular processes. TCOF1 was initially discovered as a gene involved in the Treacher Collins syndrome, a rare genetic disorder characterized by severe craniofacial deformations. Later studies revealed that treacle regulates ribosome biogenesis, mitosis, proliferation, DNA damage response, and apoptosis. Importantly, several reports indicate that treacle is also involved in cancer development, progression, and response to therapies, and may contribute to other pathologies such as Hirschsprung disease. In this manuscript, we comprehensively review the structure, function, and the regulation of TCOF1\/treacle in physiological and pathological processes.<\/jats:p>","DOI":"10.3390\/ijms22052482","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T22:02:20Z","timestamp":1614636140000},"page":"2482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["The Role of TCOF1 Gene in Health and Disease: Beyond Treacher Collins Syndrome"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2553-0166","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Grzanka","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5348-0760","authenticated-orcid":false,"given":"Agnieszka","family":"Piekie\u0142ko-Witkowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1700233","DOI":"10.1002\/bies.201700233","article-title":"New Roles for the Nucleolus in Health and Disease","volume":"40","author":"Wong","year":"2018","journal-title":"Bioessays"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.18632\/aging.101922","article-title":"Impaired ribosome biogenesis: Mechanisms and relevance to cancer and aging","volume":"11","author":"Turi","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Correll, C.C., Bartek, J., and Dundr, M. (2019). The Nucleolus: A Multiphase Condensate Balancing Ribosome Synthesis and Translational Capacity in Health, Aging and Ribosomopathies. Cells, 8.","DOI":"10.3390\/cells8080869"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1093\/emboj\/20.11.2867","article-title":"Human acrocentric chromosomes with transcriptionally silent nucleolar organizer regions associate with nucleoli","volume":"20","author":"Sullivan","year":"2001","journal-title":"EMBO J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.4161\/nucl.2.3.16246","article-title":"Assembly and disassembly of the nucleolus during the cell cycle","volume":"2","year":"2011","journal-title":"Nucleus"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1093\/nar\/26.17.3871","article-title":"The plurifunctional nucleolus","volume":"26","author":"Pederson","year":"1998","journal-title":"Nucleic Acids Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pederson, T. (2011). The nucleolus. Cold Spring Harb. Perspect Biol., 3.","DOI":"10.1101\/cshperspect.a000638"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1007\/s00018-019-03231-0","article-title":"The nucleolus: A central response hub for the stressors that drive cancer progression","volume":"76","author":"Weeks","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Penzo, M., Montanaro, L., Trer\u00e9, D., and Derenzini, M. (2019). The Ribosome Biogenesis-Cancer Connection. Cells, 8.","DOI":"10.3390\/cells8010055"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1101\/gad.333205","article-title":"The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis","volume":"19","author":"Mayer","year":"2005","journal-title":"Genes Dev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"The Treacher Collins Syndrome Collaborative Group, Dixon, J., Edwards, S.J., Gladwin, A.J., Dixon, M.J., Loftus, S.K., Bonner, C.A., Koprivnikar, K., and Wasmuth, J.J. (1996). Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. Nat. Genet., 12, 130\u2013136.","DOI":"10.1038\/ng0296-130"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3110","DOI":"10.1073\/pnas.94.7.3110","article-title":"TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region","volume":"94","author":"Wise","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/dgd.12305","article-title":"Face off against ROS: Tcof1\/Treacle safeguards neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development","volume":"58","author":"Sakai","year":"2016","journal-title":"Dev. Growth Differ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10328","DOI":"10.1038\/ncomms10328","article-title":"Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation","volume":"7","author":"Sakai","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2016.10.016","article-title":"Treacher Collins syndrome: New insights from animal models","volume":"81","author":"Tse","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_16","first-page":"907","article-title":"Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33.1","volume":"52","author":"Dixon","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1006\/geno.1993.1420","article-title":"Genetic and physical mapping of the Treacher Collins syndrome locus with respect to loci in the chromosome 5q3 region","volume":"18","author":"Jabs","year":"1993","journal-title":"Genomics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1089\/dna.2008.0766","article-title":"Regulation of the mouse Treacher Collins syndrome homolog (Tcof1) promoter through differential repression of constitutive expression","volume":"27","author":"Shows","year":"2008","journal-title":"DNA Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1101\/gr.7.3.223","article-title":"Identification of the complete coding sequence and genomic organization of the Treacher Collins syndrome gene","volume":"7","author":"Dixon","year":"1997","journal-title":"Genome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.gene.2003.11.027","article-title":"Another face of the Treacher Collins syndrome (TCOF1) gene: Identification of additional exons","volume":"328","author":"So","year":"2004","journal-title":"Gene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/ncb3007","article-title":"The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage","volume":"16","author":"Larsen","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1091\/mbc.11.9.3061","article-title":"Characterization of the nucleolar gene product, treacle, in Treacher Collins syndrome","volume":"11","author":"Isaac","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1093\/hmg\/7.11.1795","article-title":"Mutations in the Treacher Collins syndrome gene lead to mislocalization of the nucleolar protein treacle","volume":"7","author":"Marsh","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1016\/j.bbamcr.2008.07.016","article-title":"The Cajal body","volume":"1783","author":"Morris","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sakai, D., Dixon, J., Dixon, M.J., and Trainor, P.A. (2012). Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle orientation, mitotic progression, and maintenance of neural progenitor cells. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002566"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1093\/hmg\/7.12.1947","article-title":"The Treacher Collins syndrome (TCOF1) gene product, treacle, is targeted to the nucleolus by signals in its C-terminus","volume":"7","author":"Winokur","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8019","DOI":"10.1093\/nar\/gkz518","article-title":"Double-strand breaks in ribosomal RNA genes activate a distinct signaling and chromatin response to facilitate nucleolar restructuring and repair","volume":"47","author":"Korsholm","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10709","DOI":"10.1073\/pnas.0402492101","article-title":"The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor","volume":"101","author":"Valdez","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/hmg\/6.5.727","article-title":"Sequence analysis, identification of evolutionary conserved motifs and expression analysis of murine tcof1 provide further evidence for a potential function for the gene and its human homologue, TCOF1","volume":"6","author":"Dixon","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13403","DOI":"10.1073\/pnas.0603730103","article-title":"Tcof1\/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities","volume":"103","author":"Dixon","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1093\/hmg\/dds528","article-title":"Tcof1 acts as a modifier of Pax3 during enteric nervous system development and in the pathogenesis of colonic aganglionosis","volume":"22","author":"Barlow","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature14978","article-title":"Cell-fate determination by ubiquitin-dependent regulation of translation","volume":"525","author":"Werner","year":"2015","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cell.2004.11.047","article-title":"TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1","volume":"119","author":"Martin","year":"2004","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/jmcb\/mjv014","article-title":"Ribosomal proteins: Functions beyond the ribosome","volume":"7","author":"Zhou","year":"2015","journal-title":"J. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ferreira, R., Schneekloth, J.S., Panov, K.I., Hannan, K.M., and Hannan, R.D. (2020). Targeting the RNA Polymerase I Transcription for Cancer Therapy Comes of Age. Cells, 9.","DOI":"10.3390\/cells9020266"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1007\/s11427-016-0018-0","article-title":"The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity","volume":"59","author":"Xu","year":"2016","journal-title":"Sci. China Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1146\/annurev-biochem-013118-110817","article-title":"Eukaryotic Ribosome Assembly","volume":"88","author":"Hurt","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41580-018-0078-y","article-title":"Ribosome assembly coming into focus","volume":"20","author":"Klinge","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1126\/science.3413483","article-title":"Functional cooperativity between transcription factors UBF1 and SL1 mediates human ribosomal RNA synthesis","volume":"241","author":"Bell","year":"1988","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.bbrc.2009.06.050","article-title":"Treacle recruits RNA polymerase I complex to the nucleolus that is independent of UBF","volume":"386","author":"Lin","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1093\/hmg\/ddi208","article-title":"The Treacher Collins syndrome (TCOF1) gene product is involved in pre-rRNA methylation","volume":"14","author":"Gonzales","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10577-018-09603-9","article-title":"The chromatin landscape of the ribosomal RNA genes in mouse and human","volume":"27","author":"Moss","year":"2019","journal-title":"Chromosome Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Monaco, P.L., Marcel, V., Diaz, J.J., and Catez, F. (2018). 2\u2019-O-Methylation of Ribosomal RNA: Towards an Epitranscriptomic Control of Translation?. Biomolecules, 8.","DOI":"10.3390\/biom8040106"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1080\/15476286.2016.1243646","article-title":"Assembly and trafficking of box C\/D and H\/ACA snoRNPs","volume":"14","author":"Massenet","year":"2017","journal-title":"RNA Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.semcdb.2018.12.007","article-title":"Cullin 3, a cellular scripter of the non-proteolytic ubiquitin code","volume":"93","author":"Jerabkova","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Werner, A., Baur, R., Teerikorpi, N., Kaya, D.U., and Rape, M. (2018). Multisite dependency of an E3 ligase controls monoubiquitylation-dependent cell fate decisions. Elife, 7.","DOI":"10.7554\/eLife.35407"},{"key":"ref_47","first-page":"a000745","article-title":"DNA damage response","volume":"3","author":"Zotter","year":"2011","journal-title":"Cold Spring Harb. Perspect Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev.biochem.77.061306.125255","article-title":"Mechanism of eukaryotic homologous recombination","volume":"77","author":"Sung","year":"2008","journal-title":"Annu. Rev. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/jbc.R700039200","article-title":"The mechanism of human nonhomologous DNA end joining","volume":"283","author":"Lieber","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.clon.2014.02.004","article-title":"DNA double-strand break repair in a cellular context","volume":"26","author":"Shibata","year":"2014","journal-title":"Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/path.5097","article-title":"Integrating the DNA damage and protein stress responses during cancer development and treatment","volume":"246","author":"Gorgoulis","year":"2018","journal-title":"J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9449","DOI":"10.1093\/nar\/gkaa713","article-title":"Recent advances in the nucleolar responses to DNA double-strand breaks","volume":"48","author":"Korsholm","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.celrep.2016.12.035","article-title":"The Mre11-Nbs1 Interface Is Essential for Viability and Tumor Suppression","volume":"18","author":"Kim","year":"2017","journal-title":"Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"18631","DOI":"10.1073\/pnas.1422488112","article-title":"Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response","volume":"111","author":"Ciccia","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41467-019-13981-x","article-title":"Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation","volume":"11","author":"Mooser","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.cell.2005.12.041","article-title":"TopBP1 activates the ATR-ATRIP complex","volume":"124","author":"Kumagai","year":"2006","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ceb.2017.03.004","article-title":"Nucleolar reorganization in response to rDNA damage","volume":"46","author":"McStay","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1747-1028-7-3","article-title":"Polo-like kinase 1 (Plk1): An Unexpected Player in DNA Replication","volume":"7","author":"Song","year":"2012","journal-title":"Cell Div."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Nie, X., Xiao, D., Ge, Y., Xie, Y., Zhou, H., Zheng, T., Li, X., Liu, H., Huang, H., and Zhao, Y. (2020). TRF2 recruits nucleolar protein TCOF1 to coordinate telomere transcription and replication. Cell Death Differ.","DOI":"10.1038\/s41418-020-00637-3"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4232","DOI":"10.1016\/j.jmb.2020.02.004","article-title":"TERRA, a Multifaceted Regulator of Telomerase Activity at Telomeres","volume":"432","author":"Lalonde","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"245","DOI":"10.4103\/0976-237X.86480","article-title":"Franceschetti syndrome","volume":"2","author":"Kasat","year":"2011","journal-title":"Contemp Clin. Dent."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.biocel.2008.10.026","article-title":"Treacher Collins syndrome: Unmasking the role of Tcof1\/treacle","volume":"41","author":"Sakai","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.bbadis.2013.11.010","article-title":"Ribosome biogenesis in skeletal development and the pathogenesis of skeletal disorders","volume":"1842","author":"Trainor","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/ejhg.2013.98","article-title":"Large deletions encompassing the TCOF1 and CAMK2A genes are responsible for Treacher Collins syndrome with intellectual disability","volume":"22","author":"Vincent","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.bbadis.2016.03.005","article-title":"Pathogenesis of POLR1C-dependent Type 3 Treacher Collins Syndrome revealed by a zebrafish model","volume":"1862","author":"Lau","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Noack Watt, K.E., Achilleos, A., Neben, C.L., Merrill, A.E., and Trainor, P.A. (2016). The Roles of RNA Polymerase I and III Subunits Polr1c and Polr1d in Craniofacial Development and in Zebrafish Models of Treacher Collins Syndrome. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006187"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/1098-1004(200010)16:4<315::AID-HUMU4>3.0.CO;2-H","article-title":"High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes","volume":"16","author":"Splendore","year":"2000","journal-title":"Hum. Mutat."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/ng.724","article-title":"Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome","volume":"43","author":"Dauwerse","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/gim.2015.29","article-title":"Treacher Collins syndrome: A clinical and molecular study based on a large series of patients","volume":"18","author":"Vincent","year":"2016","journal-title":"Genet. Med."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Conte, C., D\u2019Apice, M.R., Rinaldi, F., Gambardella, S., Sangiuolo, F., and Novelli, G. (2011). Novel mutations of TCOF1 gene in European patients with Treacher Collins syndrome. BMC Med. Genet., 12.","DOI":"10.1186\/1471-2350-12-125"},{"key":"ref_72","first-page":"515","article-title":"The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon","volume":"60","author":"Edwards","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1136\/jmg.39.7.493","article-title":"Screening of TCOF1 in patients from different populations: Confirmation of mutational hot spots and identification of a novel missense mutation that suggests an important functional domain in the protein treacle","volume":"39","author":"Splendore","year":"2002","journal-title":"J. Med. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1093\/hmg\/5.10.1533","article-title":"Treacher Collins syndrome may result from insertions, deletions or splicing mutations, which introduce a termination codon into the gene","volume":"5","author":"Gladwin","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/humu.20159","article-title":"TCOF1 mutation database: Novel mutation in the alternatively spliced exon 6A and update in mutation nomenclature","volume":"25","author":"Splendore","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/ejhg.2008.221","article-title":"Treacher Collins syndrome: Etiology, pathogenesis and prevention","volume":"17","author":"Trainor","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6068","DOI":"10.1093\/emboj\/cdg579","article-title":"Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses","volume":"22","author":"Rubbi","year":"2003","journal-title":"EMBO J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1182\/blood.2019003439","article-title":"p53 activation during ribosome biogenesis regulates normal erythroid differentiation","volume":"137","author":"Boussaid","year":"2021","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1016\/j.febslet.2014.04.014","article-title":"p53 and ribosome biogenesis stress: The essentials","volume":"588","author":"Golomb","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1101\/gad.189951.112","article-title":"Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2\/M checkpoint","volume":"26","author":"Fumagalli","year":"2012","journal-title":"Genes Dev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1042\/BST20160106","article-title":"The importance of ribosome production, and the 5S RNP-MDM2 pathway, in health and disease","volume":"44","author":"Pelava","year":"2016","journal-title":"Biochem Soc. Trans."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nm1725","article-title":"Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function","volume":"14","author":"Jones","year":"2008","journal-title":"Nat. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5930","DOI":"10.1128\/MCB.20.16.5930-5938.2000","article-title":"Repression of RNA polymerase I transcription by the tumor suppressor p53","volume":"20","author":"Zhai","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e2397","DOI":"10.1038\/cddis.2016.299","article-title":"Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes","volume":"7","author":"Mouguelar","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Masotti, C., Ornelas, C.C., Splendore-Gordonos, A., Moura, R., F\u00e9lix, T.M., Alonso, N., Camargo, A.A., and Passos-Bueno, M.R. (2009). Reduced transcription of TCOF1 in adult cells of Treacher Collins syndrome patients. BMC Med. Genet., 10.","DOI":"10.1186\/1471-2350-10-136"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1097\/SCS.0000000000002719","article-title":"Tcof1-Related Molecular Networks in Treacher Collins Syndrome","volume":"27","author":"Dai","year":"2016","journal-title":"J. Craniofac Surg."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.bbrc.2018.10.060","article-title":"DDX21 promotes gastric cancer proliferation by regulating cell cycle","volume":"505","author":"Cao","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature25449","article-title":"Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders","volume":"554","author":"Calo","year":"2018","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1002\/pmic.201000020","article-title":"SILAC analysis of oxidative stress-mediated proteins in human pneumocytes: New role for treacle","volume":"10","author":"Duan","year":"2010","journal-title":"Proteomics"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3109\/10715761003667554","article-title":"Reactive oxygen species in cancer","volume":"44","author":"Liou","year":"2010","journal-title":"Free Radic. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.7150\/thno.39341","article-title":"Copy Number Amplification of DNA Damage Repair Pathways Potentiates Therapeutic Resistance in Cancer","volume":"10","author":"Wu","year":"2020","journal-title":"Theranostics"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"32505","DOI":"10.1074\/jbc.M501449200","article-title":"Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase\/Akt","volume":"280","author":"Chen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/sj.onc.1209929","article-title":"Overexpression of NBS1 induces epithelial-mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer","volume":"26","author":"Yang","year":"2007","journal-title":"Oncogene"},{"key":"ref_94","first-page":"99","article-title":"DNA damage response: The players, the network and the role in tumor suppression","volume":"4","author":"Rai","year":"2007","journal-title":"Cancer Genom. Proteom."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev-med-081313-121208","article-title":"The DNA damage response: Implications for tumor responses to radiation and chemotherapy","volume":"66","author":"Goldstein","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1667\/RR15342.1","article-title":"Stable Acinar Progenitor Cell Model Identifies Treacle-Dependent Radioresistance","volume":"192","author":"Weber","year":"2019","journal-title":"Radiat. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e478s","DOI":"10.6061\/clinics\/2018\/e478s","article-title":"DNA repair pathways and cisplatin resistance: An intimate relationship","volume":"73","author":"Rocha","year":"2018","journal-title":"Clinics"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"27519","DOI":"10.18632\/oncotarget.4823","article-title":"Depletion of the cisplatin targeted HMGB-box factor UBF selectively induces p53-independent apoptotic death in transformed cells","volume":"6","author":"Hamdane","year":"2015","journal-title":"Oncotarget"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1007\/s00018-009-9154-y","article-title":"Protein kinase CK2 in health and disease: CK2: A key player in cancer biology","volume":"66","author":"Trembley","year":"2009","journal-title":"Cell Mol. Life Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/leu.2017.301","article-title":"Therapeutic targeting of CK2 in acute and chronic leukemias","volume":"32","author":"Buontempo","year":"2018","journal-title":"Leukemia"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s13046-019-1292-y","article-title":"Role of protein kinase CK2 in antitumor drug resistance","volume":"38","author":"Borgo","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1038\/s41467-018-06287-x","article-title":"Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination","volume":"9","author":"Gustafsson","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1042\/BST20190854","article-title":"MicroRNAs and long non-coding RNAs as novel regulators of ribosome biogenesis","volume":"48","author":"McCool","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bcp.2018.11.014","article-title":"Ribosome biogenesis: An emerging druggable pathway for cancer therapeutics","volume":"159","author":"Catez","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/ncb1144","article-title":"HIF activation by pH-dependent nucleolar sequestration of VHL","volume":"6","author":"Mekhail","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.molcel.2011.12.012","article-title":"Immobilization of proteins in the nucleolus by ribosomal intergenic spacer noncoding RNA","volume":"45","author":"Audas","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ydbio.2012.02.035","article-title":"Neural crest progenitors and stem cells: From early development to adulthood","volume":"366","author":"Dupin","year":"2012","journal-title":"Dev. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2482\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:31:08Z","timestamp":1760160668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":107,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22052482"],"URL":"https:\/\/doi.org\/10.3390\/ijms22052482","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,1]]}}}