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Updated: Jun 24, 2025

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
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A PRMT5-ZNF326 axis mediates innate immune activation upon replication stress

Phuong Mai Hoang1, Denis Torre2,3,4, Patrick Jaynes1

  • 1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

Science Advances
|June 5, 2024
PubMed

Insights

Protein arginine methyltransferase 5 (PRMT5) mediates DNA replication stress responses by inducing interferon-stimulated genes (ISGs) and reactivating endogenous retroviruses (ERVs). PRMT5 regulates ZNF326, impacting cancer therapy and homeostasis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • DNA replication stress (RS) is a hallmark of cancer, leading to genomic instability and chromatin changes.
  • DNA damage triggers innate immune signaling, but the regulators involved in replication stress responses are poorly understood.

Purpose of the Study:

  • To identify transcriptional regulators mediating innate immune signaling during DNA replication stress.
  • To elucidate the role of protein arginine methyltransferase 5 (PRMT5) in replication stress-induced gene expression.

Main Methods:

  • Chemical screening to identify key mediators of replication stress response.
  • Quantitative mass spectrometry to identify proteins with symmetric dimethylarginine (SDMA) modifications.
  • Functional assays to assess the role of PRMT5 and ZNF326 in interferon-stimulated gene (ISG) induction.

Main Results:

  • PRMT5 was identified as a crucial mediator of RS-dependent induction of interferon-stimulated genes (ISGs).
  • RS induces PRMT5-dependent symmetric dimethylarginine (SDMA) modifications on specific proteins.
  • PRMT5 directly targets and modulates the activity of ZNF326, a key factor in ISG response.

Conclusions:

  • PRMT5-mediated SDMA plays a significant role in transcriptional induction during replication stress.
  • This pathway impacts physiological homeostasis and has implications for cancer therapy.
  • PRMT5 is a potential therapeutic target for managing replication stress in cancer.

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