{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Korsholm LM"],"funding":["Innovation Fund Denmark","Steno Diabetes Center Aarhus (SDCA)","Danish Research Council for Independent Research","Danish Cancer Society","Lundbeck Foundation"],"pagination":["8019-8035"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6735822"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["47(15)"],"pubmed_abstract":["The nucleolus is a nuclear sub-domain containing the most highly transcribed genes in the genome. Hundreds of human ribosomal RNA (rRNA) genes, located in the nucleolus, rely on constant maintenance. DNA double-strand breaks (DSBs) in rRNA genes activate the ATM kinase, repress rRNA transcription and induce nucleolar cap formation. Yet how ribosomal-DNA (rDNA) lesions are detected and processed remains elusive. Here, we use CRISPR/Cas9-mediated induction of DSBs and report a chromatin response unique to rDNA depending on ATM-phosphorylation of the nucleolar protein TCOF1 and recruitment of the MRE11-RAD50-NBS1 (MRN) complex via the NBS1-subunit. NBS1- and MRE11-depleted cells fail to suppress rRNA transcription and to translocate rDNA into nucleolar caps. Furthermore, the DNA damage respon"],"journal":["Nucleic acids research"],"pubmed_title":["Double-strand breaks in ribosomal RNA genes activate a distinct signaling and chromatin response to facilitate nucleolar restructuring and repair."],"pmcid":["PMC6735822"],"funding_grant_id":["R209-A12925","R219-2016-1375","6110-00506A","DFF-1337-00128","R146-A9403","R192-2015-335","R173-2014-1105","308","309","DFF-1335-00763A"],"pubmed_authors":["Bartek J","Dulina E","Korsholm LM","Gal Z","Quevedo O","Luo Y","Lin L","Ahmad DA","Larsen DH"],"additional_accession":[]},"is_claimable":false,"name":"Double-strand breaks in ribosomal RNA genes activate a distinct signaling and chromatin response to facilitate nucleolar restructuring and repair.","description":"The nucleolus is a nuclear sub-domain containing the most highly transcribed genes in the genome. Hundreds of human ribosomal RNA (rRNA) genes, located in the nucleolus, rely on constant maintenance. DNA double-strand breaks (DSBs) in rRNA genes activate the ATM kinase, repress rRNA transcription and induce nucleolar cap formation. Yet how ribosomal-DNA (rDNA) lesions are detected and processed remains elusive. Here, we use CRISPR/Cas9-mediated induction of DSBs and report a chromatin response unique to rDNA depending on ATM-phosphorylation of the nucleolar protein TCOF1 and recruitment of the MRE11-RAD50-NBS1 (MRN) complex via the NBS1-subunit. NBS1- and MRE11-depleted cells fail to suppress rRNA transcription and to translocate rDNA into nucleolar caps. Furthermore, the DNA damage respon","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Sep","modification":"2026-05-04T21:00:50.734Z","creation":"2026-04-07T20:55:59.339Z"},"accession":"S-EPMC6735822","cross_references":{"pubmed":["31184714"],"doi":["10.1093/nar/gkz518"]}}