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Updated: May 20, 2026
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Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications
Published on: April 21, 2023
Treacle-dependent TOPBP1 condensation regulates the nucleolar DNA damage response
Nadezhda V Petrova1, Dmitry A Deriglazov1, Anastasia P Kovina1
1Department of Cellular Genomics, Institute of Gene Biology RAS, 119334 Moscow, Russia.
Nucleic Acids Research
|May 19, 2026
Summary
Treacle protein drives TOPBP1 condensation in the nucleolus, creating a signaling platform crucial for maintaining ribosomal DNA (rDNA) stability and coordinating DNA repair pathways.
Area of Science:
- Molecular Biology
- Genetics
- Cellular Biology
Background:
- Ribosomal DNA (rDNA) arrays are highly transcribed repetitive genomic regions requiring specialized mechanisms for stability.
- The nucleolar DNA damage response (n-DDR) is essential for rDNA integrity, involving the scaffold protein TOPBP1 and fibrillar center protein Treacle.
Purpose of the Study:
- To investigate the role of Treacle in promoting TOPBP1 phase separation within the nucleolar fibrillar center.
- To elucidate how Treacle-mediated TOPBP1 condensation influences nucleolar DNA damage response signaling and rDNA repair pathway engagement.
Main Methods:
- Utilized an inducible TOPBP1 oligomerization system in physiological models of rDNA damage.
- Investigated the effects of Treacle phosphorylation by CK2 and ATR/ATM on TOPBP1 interaction and condensation.
- Analyzed DNA repair pathway engagement, signaling dynamics (ATR/ATM, γH2AX), and recruitment of repair factors in wild-type and Treacle-knockout cells.
Main Results:
- Treacle promotes TOPBP1 phase separation and condensation within the nucleolar fibrillar center, establishing a signaling platform.
- Treacle-dependent TOPBP1 condensation enhances ATR/ATM activation, γH2AX signaling, and DNA repair factor recruitment.
- Disruption of this process shifts rDNA double-strand break repair towards DNA-PK-dependent nonhomologous end joining, attenuating homologous recombination pathways.
Conclusions:
- Treacle-dependent TOPBP1 condensation acts as a critical nucleolar signaling hub for rDNA integrity.
- This mechanism is vital for coordinating DNA repair pathways to ensure accurate maintenance of repetitive rDNA arrays.
- Treacle knockout cells show altered DNA repair kinetics, highlighting the importance of this condensation process for long-term rDNA stability.
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