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.

Nucleic Acids Research
|January 20, 2021
PubMed

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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