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Cell-Cycle-Dependent Chromatin Dynamics at Replication Origins.

Yulong Li1, Alexander J Hartemink1, David M MacAlpine2

  • 1Department of Computer Science, Duke University, Durham, NC 27708, USA.

Genes
|December 24, 2021
PubMed
Summary
This summary is machine-generated.

DNA replication origins are regulated by cell-cycle-dependent chromatin changes. Studies show nucleosome repositioning and pre-replicative complex assembly in G1, with CMG complex formation in S phase determining origin efficiency.

Keywords:
DNA replicationcell cyclechromatinreplication origins

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • DNA replication origin specification involves ordered, cell-cycle-dependent recruitment of replication factors.
  • Pre-replicative complex (pre-RC) assembly in G1 and pre-initiation complex formation before S phase are known.
  • The interplay between these complex assemblies and the local chromatin environment remains less understood.

Purpose of the Study:

  • To investigate dynamic chromatin organization changes at and around DNA replication origins.
  • To understand how chromatin dynamics influence replication origin activity throughout the cell cycle.

Main Methods:

  • Utilized micrococcal nuclease (MNase) for genome-wide chromatin occupancy profiling in *Saccharomyces cerevisiae*.
  • Monitored nucleosomes, transcription factors, and replication proteins across consecutive cell cycles.
  • Analyzed DNA fragments to assess pre-RC assembly and origin efficiency.

Main Results:

  • Observed downstream repositioning of the +1 nucleosome and increased protected DNA fragments at the ARS consensus sequence (ACS) during G1, indicating pre-RC assembly.
  • Found the strongest correlation between ACS chromatin occupancy and origin efficiency in early S phase, linked to CMG complex formation.
  • Detected nucleosome disruption and disorganization spreading from origins with elongating replication forks during S phase.

Conclusions:

  • Cell-cycle-regulated chromatin dynamics, including nucleosome repositioning and disruption, are crucial for DNA replication origin firing.
  • The formation of the CMG complex is a key determinant of origin activity.
  • Replication forks are associated with dynamic chromatin remodeling, involving disassembly and assembly processes.