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Visualization and quantification of rDNA instabilities in mammalian cells and mouse models
Xiaolu Zhu1, Wenxia Jiang1,2, Wei Wu3
1Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY 10032, United States.
Nucleic Acids Research
|January 14, 2026
Summary
Researchers developed new tools to study ribosomal DNA (rDNA) instability in mice. This instability is linked to aging and cancer, and the new methods reveal its complex nature in cells and animals.
Area of Science:
- Genetics
- Molecular Biology
- Genomics
Background:
- Ribosomal DNA (rDNA) is crucial for cell function, accounting for significant transcription.
- Quantifying rDNA instability in mammals is difficult due to its repetitive nature.
- rDNA instability is implicated in aging and cancer.
Purpose of the Study:
- To develop tools for quantifying rDNA instability in laboratory mice.
- To investigate the sources and mechanisms of rDNA instability in mammalian cells.
- To establish a platform for studying rDNA-related diseases in animal models.
Main Methods:
- Developed a murine rDNA Fluorescence In Situ Hybridization (FISH) probe and genomic tools.
- Analyzed rDNA organization and heterogeneity in various mouse strains and cell types.
- Investigated the roles of DNA repair pathways (homologous recombination, non-homologous end joining) and kinases (ATM) in rDNA stability using mouse embryonic stem cells.
Main Results:
- Confirmed rDNA cluster locations in mice.
- Revealed significant inter- and intra-strain, and intercellular heterogeneity in rDNA organization.
- Identified DNA double-strand breaks in the rDNA transcription termination region.
- Showed BRCA1 promotes rDNA instability, XRCC1 suppresses intra-cluster deletions, and ATM preserves rDNA stability.
Conclusions:
- Established a robust platform and essential tools for studying rDNA instability in mammalian models.
- Provided new insights into the complex regulation of rDNA stability and its relationship with DNA repair pathways.
- Opened avenues for research into aging and cancer pathogenesis linked to rDNA instability.
