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Histone acetyltransferase 1 is required for DNA replication fork function and stability.

Paula A Agudelo Garcia1, Callie M Lovejoy1, Prabakaran Nagarajan1

  • 1Department of Biological Chemistry and Pharmacology, the Ohio State University, Columbus, Ohio, USA.

The Journal of Biological Chemistry
|May 6, 2020
PubMed
Summary
This summary is machine-generated.

Histone acetyltransferase 1 (HAT1) is crucial for DNA replication fork stability and chromatin assembly. Its absence leads to replication fork stalling, instability, and DNA degradation, highlighting its role in histone processing.

Keywords:
DNA replicationHAT1acetylationacetyltransferasechromatinchromatin assemblyhistone acetylasereplication forkreplication fork stallingreplication stress

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • DNA Replication

Background:

  • The replisome orchestrates DNA replication at the dynamic intersection of parental and nascent chromatin.
  • Replication-coupled chromatin assembly involves disrupting parental nucleosomes and packaging daughter DNA with new and old histones.
  • Histone acetyltransferase 1 (HAT1) performs cytosolic diacetylation of newly synthesized histone H4, a key step in chromatin assembly.

Purpose of the Study:

  • To investigate the role of murine Histone acetyltransferase 1 (HAT1) in replication-coupled chromatin assembly.
  • To analyze the physical association of HAT1 with chromatin during DNA replication.

Main Methods:

  • Proximity ligation assay-based chromatin assembly assays.
  • DNA fiber analysis to study replication fork dynamics.
  • Analysis of HAT1 association with newly replicated DNA and nascent chromatin.

Main Results:

  • HAT1 physically associates with chromatin near DNA replication sites, with transient binding stabilized by replication fork stalling.
  • Loss of HAT1 function impairs replication fork progression and increases stalling.
  • In HAT1-deficient cells, stalled replication forks are unstable, leading to MRE11-dependent degradation of newly synthesized DNA.

Conclusions:

  • HAT1 plays a critical role in maintaining replication fork stability and integrity.
  • HAT1 links DNA replication fork progression to the correct processing and assembly of newly synthesized histones.
  • The findings reveal a novel function for HAT1 in safeguarding newly replicated DNA from degradation.