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

Mar 7, 2025Nucleic acids research

Checkpoint kinases influence the body’s internal clock after DNA damage by changing how DNA is packaged

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Abstract

CHK1/2 are essential for maintaining robust circadian rhythms during DNA damage stress.

  • Deletion of chk1/2 disrupted the rhythmic transcription of the clock gene frq under DNA damage stress.
  • CHK1/2 regulate chromatin structure by interacting with the transcription activator White Collar complex (WCC) at the frq promoter.
  • Phosphorylation of H3T11 by CHK1/2 promotes H3 acetylation, particularly H3K56 acetylation, to counteract histone variant H2A.Z deposition.
  • A genome-wide correlation exists between H3T11 phosphorylation and H3K56 acetylation, specifically at the frq promoter dependent on CHK1/2.
  • CHK1/2 are linked to the rhythmic transcription of metabolic and DNA repair genes during DNA damage.

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