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The results confirmed rDNA cluster locations, revealed substantial inter- and intra-strain as well as intercellular heterogeneity in rDNA organization within inbred mice and unstressed cells, and identified sources of spontaneous and replication-associated DNA double-strand breaks in the rDNA transcription termination region. Using mouse embryonic stem cells, we showed that BRCA1-mediated homologous recombination promotes rDNA instability, the non-homologous end joining factor XRCC1, but not Ku, suppresses intra-cluster deletions, and ATM kinase preserves rDNA cluster stability. Together, these findings establish a platform and tools for studying rDNA instability in animal models relevant to aging and cancer research.<\/jats:p>","DOI":"10.1093\/nar\/gkaf1523","type":"journal-article","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T12:35:54Z","timestamp":1766838954000},"source":"Crossref","is-referenced-by-count":1,"title":["Visualization and quantification of rDNA instabilities in mammalian cells and mouse models"],"prefix":"10.1093","volume":"54","author":[{"given":"Xiaolu","family":"Zhu","sequence":"first","affiliation":[{"name":"Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxia","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]},{"name":"Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5164-2765","authenticated-orcid":false,"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"The Laboratory of Genome Integrity, National Cancer Institute, NIH , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demis","family":"Menolfi","sequence":"additional","affiliation":[{"name":"Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Tubbs","sequence":"additional","affiliation":[{"name":"The Laboratory of Genome Integrity, National Cancer Institute, NIH , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia M","family":"Cupo","sequence":"additional","affiliation":[{"name":"Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Malkovskiy","sequence":"additional","affiliation":[{"name":"Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United 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States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chyuan-Sheng V","family":"Lin","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1519-4800","authenticated-orcid":false,"given":"Lorraine","family":"Symington","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Nussenzweig","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United 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Cell Transplantation, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]},{"name":"Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University , New York City, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"2026011413131338400_B1","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1182\/blood-2009-10-178129","article-title":"Ribosomopathies: human disorders of ribosome dysfunction","volume":"115","author":"Narla","year":"2010","journal-title":"Blood"},{"key":"2026011413131338400_B2","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.semcdb.2022.04.001","article-title":"Nucleolar stress: from development to cancer","volume":"136","author":"Lafita-Navarro","year":"2023","journal-title":"Semin Cell 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