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Updated: Nov 20, 2025

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Published on: April 28, 2021
A DYRK1B-dependent pathway suppresses rDNA transcription in response to DNA damage
Chao Dong1, Liwei An1, Cheng-Han Yu1
1School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong S.A.R.
Abstract:
DNA double-strand breaks (DSBs) at ribosomal gene loci trigger inhibition of ribosomal DNA (rDNA) transcription and extensive nucleolar reorganization, including the formation of nucleolar caps where rDNA DSBs engage with canonical DSB signaling and repair factors. While these nucleolar responses underlie maintenance of rDNA stability, the molecular components that drive each of these events remain to be defined. Here we report that full suppression of rRNA synthesis requires the DYRK1B kinase, a nucleolar DSB response that can be uncoupled from ATM-mediated DSB signaling events at the nucleolar periphery. Indeed, by targeting DSBs onto rDNA arrays, we uncovered that chemical inhibition or genetic inactivation of DYRK1B led to sustained nucleolar transcription. Not only does DYRK1B exhibit robust nucleolar accumulation following laser micro-irradiation across cell nuclei, we further showed that DYRK1B is required for rDNA DSB repair and rDNA copy number maintenance, and that DYRK1B-inactivated cells are hypersensitised to DSBs induced at the rDNA arrays. Together, our findings not only identify DYRK1B as a key signaling intermediate that coordinates DSB repair and rDNA transcriptional activities, but also support the idea of specialised DSB responses that operate within the nucleolus to preserve rDNA integrity.
Insights
DYRK1B kinase is essential for suppressing ribosomal DNA transcription after DNA double-strand breaks (DSBs). This kinase also plays a crucial role in DNA double-strand break repair and maintaining ribosomal DNA stability.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- DNA double-strand breaks (DSBs) at ribosomal gene loci induce nucleolar reorganization and inhibit ribosomal DNA (rDNA) transcription.
- These nucleolar responses are critical for maintaining rDNA stability, but the underlying molecular mechanisms are not fully understood.
Purpose of the Study:
- To identify the molecular components responsible for inhibiting rDNA transcription and maintaining rDNA stability following DSBs.
- To investigate the role of DYRK1B kinase in the nucleolar response to DSBs.
Main Methods:
- Targeting DSBs to rDNA arrays using laser micro-irradiation.
- Chemical inhibition and genetic inactivation of DYRK1B.
- Monitoring rRNA synthesis and nucleolar reorganization.
- Assessing DYRK1B localization and accumulation in the nucleolus.
Main Results:
- DYRK1B kinase is required for the full suppression of rRNA synthesis upon rDNA DSBs.
- DYRK1B accumulates in the nucleolus following laser-induced DSBs.
- DYRK1B inhibition or inactivation leads to sustained rDNA transcription and hypersensitivity to rDNA DSBs.
- DYRK1B is essential for rDNA DSB repair and maintaining rDNA copy number.
Conclusions:
- DYRK1B acts as a key signaling intermediate coordinating DSB repair and rDNA transcriptional activity within the nucleolus.
- Specialized DSB responses within the nucleolus are crucial for preserving rDNA integrity.
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