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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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DYRK2 maintains genome stability via neddylation of cullins in response to DNA damage

Akira Kawamura1, Saishu Yoshida1, Katsuhiko Aoki1

  • 1Department of Biochemistry, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.

Journal of Cell Science
|May 18, 2022
PubMed

Insights

Dual-specificity tyrosine-regulated kinase 2 (DYRK2) regulates neddylation, a process crucial for DNA damage response. Its absence causes DNA breaks and genome instability, highlighting DYRK2

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • Neural precursor cell-expressed developmentally down-regulated 8 (NEDD8) is vital for DNA damage response.
  • Dysfunctional neddylation is linked to human diseases, including cancer.
  • Understanding neddylation regulation is key to genome stability and carcinogenesis mechanisms.

Purpose of the Study:

  • To identify novel regulators of neddylation.
  • To investigate the role of dual-specificity tyrosine-regulated kinase 2 (DYRK2) in neddylation and genome stability.
  • To elucidate the mechanism by which DYRK2 influences neddylation.

Main Methods:

  • Investigated the role of DYRK2 in neddylation.
  • Assessed the impact of DYRK2 deletion on DNA double-strand breaks (DSBs) and genome stability.
  • Examined the molecular mechanism of DYRK2's interaction with NAE1 and its effect on polyubiquitylation.

Main Results:

  • DYRK2 was identified as a novel regulator of neddylation.
  • DYRK2 deletion resulted in persistent DSBs and compromised genome stability.
  • DYRK2 interacts with NAE1, a component of the NEDD8-activating enzyme E1, and suppresses its polyubiquitylation, thereby maintaining its protein levels and promoting neddylation.

Conclusions:

  • DYRK2 is essential for controlling neddylation.
  • DYRK2 plays a critical role in maintaining genome stability.
  • This study provides the first evidence that DYRK2 regulates neddylation and is necessary for genome stability.
Keywords:
DNA damage responseDNA double-strand breaksDYRK2Genome stabilityNEDD8Neddylation

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