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Phosphorylation of DNA-binding domains of CLOCK–BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells
How adding phosphate to CLOCK-BMAL1 controls PER-based inhibition in the body’s daily clock
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Abstract
Nonphosphorylatable mutations at CLOCK-Ser38 and Ser42 shorten the circadian period, while phospho-mimetic mutations abolish circadian rhythms.
- CLOCK and BMAL1 proteins interact to regulate gene transcription linked to circadian rhythms.
- Phosphorylation at CLOCK-Ser38 and Ser42 is crucial for proper circadian clock function.
- Knockout rescue experiments indicate that specific mutations can disrupt normal circadian oscillation.
- Mathematical modeling suggests that phospho-mimetic mutations impair DNA binding of the CLOCK-BMAL1 complex.
- Biochemical experiments confirm that phosphorylation sites are important for the displacement of the CLOCK-BMAL1 complex during inhibition by PER2.
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