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Mol Cell. 2017 Jul 20;67(2):203-213.e4. doi: 10.1016/j.molcel.2017.05.029. Epub 2017 Jun 22.

DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.

Author information

1
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA.
2
Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH 45267, USA.
3
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA; Department of Biochemistry and Cell Biology, McMurtry College, Rice University, Houston, TX 77005, USA.
4
State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
5
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA. Electronic address: yi.liu@utsouthwestern.edu.

Abstract

Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of the circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in the circadian mechanism.

KEYWORDS:

DNA replication; cell cycle; circadian clock; histone H2A.Z; nucleosome composition

Comment in

PMID:
28648778
PMCID:
PMC5543814
DOI:
10.1016/j.molcel.2017.05.029
[Indexed for MEDLINE]
Free PMC Article

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