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Checkpoint kinases regulate the circadian clock after DNA damage by influencing chromatin dynamics

Yulin Yang1,2, Zeyu Duan1, Xiao-Lan Liu1

  • 1State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Nucleic Acids Research
|March 7, 2025
PubMed

Insights

Checkpoint kinases CHK1/2 maintain circadian rhythms during DNA damage by regulating chromatin structure. These kinases ensure rhythmic gene transcription, crucial for cellular health under stress.

Area of Science:

  • Chronobiology
  • Molecular Biology
  • Epigenetics

Background:

  • The relationship between circadian clocks, cell cycle, and DNA repair is known.
  • Epigenetic regulation of circadian clocks by DNA damage responses is less understood.

Purpose of the Study:

  • Investigate the role of checkpoint kinases in epigenetic control of circadian rhythms during DNA damage.
  • Elucidate the mechanism by which DNA damage responses maintain circadian rhythms.

Main Methods:

  • Utilized Neurospora crassa as a model organism.
  • Performed gene deletion studies (chk1/2).
  • Analyzed gene transcription, protein binding (WCC), chromatin structure, and histone modifications (H3T11 phosphorylation, H3 acetylation, H2A.Z deposition).
  • Conducted genome-wide correlation analysis and transcriptome analysis.

Main Results:

  • Deletion of CHK1/2 disrupted rhythmic transcription of the clock gene frq under DNA damage.
  • CHK1/2 regulate chromatin structure at the frq promoter by promoting H3T11 phosphorylation and H3 acetylation, counteracting H2A.Z deposition.
  • CHK1/2 are essential for the rhythmic transcription of metabolic and DNA repair genes during DNA damage.

Conclusions:

  • Checkpoint kinases CHK1/2 play a critical role in maintaining robust circadian rhythms under DNA damage stress.
  • CHK1/2 coordinate epigenetic modifications to ensure appropriate chromatin states for circadian gene expression.
  • This study reveals a novel mechanism linking DNA damage response pathways to circadian clock regulation.

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