{"entity": "publication", "iuid": "2c59cc8996af4c6abab3d4030d2827d9", "timestamp": "2026-08-29T04:17:33.262Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2c59cc8996af4c6abab3d4030d2827d9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2c59cc8996af4c6abab3d4030d2827d9"}}, "title": "Double-strand breaks in ribosomal RNA genes activate a distinct signaling and chromatin response to facilitate nucleolar restructuring and repair.", "authors": [{"family": "Korsholm", "given": "Lea M", "initials": "LM"}, {"family": "G\u00e1l", "given": "Zita", "initials": "Z"}, {"family": "Lin", "given": "Lin", "initials": "L"}, {"family": "Quevedo", "given": "Oliver", "initials": "O"}, {"family": "Ahmad", "given": "Diana A", "initials": "DA"}, {"family": "Dulina", "given": "Ekaterina", "initials": "E"}, {"family": "Luo", "given": "Yonglun", "initials": "Y"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Larsen", "given": "Dorthe H", "initials": "DH"}], "type": "journal article", "published": "2019-09-05", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "47", "issue": "15", "pages": "8019-8035", "issn-l": "0305-1048"}, "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 response (DDR) kinase ATR operates downstream of the ATM-TCOF1-MRN interplay and is required to fully suppress rRNA transcription and complete DSB-induced nucleolar restructuring. Unexpectedly, we find that DSBs in rDNA neither activate checkpoint kinases CHK1/CHK2 nor halt cell-cycle progression, yet the nucleolar-DDR protects against genomic aberrations and cell death. Our data highlight the concept of a specialized nucleolar DNA damage response (n-DDR) with a distinct protein composition, spatial organization and checkpoint communication. The n-DDR maintains integrity of ribosomal RNA genes, with implications for cell physiology and disease.", "doi": "10.1093/nar/gkz518", "pmid": "31184714", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6735822"}, {"db": "pii", "key": "5513781"}], "notes": [], "created": "2026-08-20T09:50:38.859Z", "modified": "2026-08-20T09:50:38.873Z"}