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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
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The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
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Chromosome Replication02:31

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Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
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DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.

Xiao Liu1, Yunkun Dang1, Toru Matsu-Ura2

  • 1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA.

Molecular Cell
|June 27, 2017
PubMed
Summary
This summary is machine-generated.

DNA replication is essential for circadian clock function in Neurospora, regulating frequency (frq) gene transcription and nucleosome dynamics. This research reveals a critical interdependence between the cell cycle and circadian rhythms.

Keywords:
DNA replicationcell cyclecircadian clockhistone H2A.Znucleosome composition

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Area of Science:

  • Chronobiology
  • Molecular Biology
  • Genetics

Background:

  • Circadian clocks regulate daily rhythms, gating cell division and DNA replication.
  • Circadian clock function was previously thought to be independent of the cell cycle.

Purpose of the Study:

  • To investigate the role of DNA replication in circadian clock function in Neurospora.
  • To elucidate the molecular mechanisms linking cell cycle and circadian clock.

Main Methods:

  • Genetic and pharmacological inhibition of DNA replication.
  • Analysis of gene transcription (frequency gene) and molecular rhythms.
  • Chromatin immunoprecipitation to assess nucleosome composition at the frequency promoter.
  • Investigating the role of the FACT complex and histone variants (H2A.Z).

Main Results:

  • Inhibition of DNA replication abolished circadian rhythms and repressed frequency (frq) gene transcription.
  • DNA replication is critical for rhythmic nucleosome composition changes at the frq promoter.
  • The FACT complex is recruited to the frq promoter in a replication-dependent manner, facilitating histone exchange.
  • Deletion of H2A.Z disrupted the dependence of the circadian clock on DNA replication.

Conclusions:

  • DNA replication is required for circadian clock function in Neurospora.
  • Establishes a critical interdependence between the circadian clock and cell cycle oscillators.
  • Identifies DNA replication as a key process in the circadian mechanism, involving chromatin remodeling at the frq promoter.