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Updated: Jun 29, 2025

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique
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Acute multi-level response to defective de novo chromatin assembly in S-phase

Jan Dreyer1, Giulia Ricci1, Jeroen van den Berg1,2

  • 1Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.

Biorxiv : the Preprint Server for Biology
|April 8, 2024
PubMed

Insights

Defects in new chromatin assembly (CAF-1) during DNA replication slow replication speed and trigger a rapid cellular response. This impacts histone levels and chromatin maturation, leading to cell-cycle arrest and altered epigenome maintenance.

Area of Science:

  • Cell Biology
  • Epigenetics
  • Genomics

Background:

  • Long-term disruption of new chromatin assembly during DNA replication affects epigenome maintenance and cell fate.
  • The precise early mechanisms driving these defects remain unclear.

Approach:

  • Utilized acute degradation of Chromatin Assembly Factor 1 (CAF-1) in human cells.
  • Employed single-cell genomics, quantitative proteomics, and live-microscopy to investigate initial mechanisms.
  • Focused on the immediate consequences of CAF-1 loss during DNA replication.

Key Points:

  • CAF-1 loss decelerates DNA replication and increases nascent DNA accessibility.
  • A novel cellular response, separate from DNA damage signaling, reduces histone mRNA levels.
  • Altered histone variant usage and modifications impair transcriptional fidelity and chromatin maturation within one S-phase.

Conclusions:

  • Defective new chromatin assembly during replication triggers rapid, multi-level cellular responses.
  • These immediate effects lead to cell-cycle arrest post-mitosis.
  • The study elucidates how initial defects in chromatin assembly propagate to alter the epigenome and cell fate over time.
Keywords:
DNA replicationcell cyclechromatin assemblyepigenome stabilityhistone chaperones

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