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

Checkpoint kinases 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.

Simplified