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Updated: Jan 23, 2026

Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on TRO Approach
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Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on TRO Approach

Published on: March 12, 2017

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Transcription termination counteracts DNA damage after WEE1 inhibition

Helga B Landsverk1, Lise E Sandquist1, Lilli T E Bay1

  • 1Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway.

Nucleic Acids Research
|January 22, 2026
PubMed

Insights

Transcription termination prevents DNA damage during cancer therapy. Inhibiting termination factors increases DNA damage when WEE1 is blocked, suggesting new therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Cancer Therapeutics
  • DNA Damage Response

Background:

  • Transcription termination is a critical regulatory process in gene expression.
  • Understanding transcription termination's role in cancer therapy is essential.
  • WEE1 inhibition by adavosertib can induce DNA damage, but the underlying mechanisms require further elucidation.

Purpose of the Study:

  • To investigate the role of transcription termination in mitigating DNA damage induced by WEE1 inhibition.
  • To explore the therapeutic potential of targeting transcription termination in combination with WEE1 inhibitors.

Main Methods:

  • Depletion of transcription termination factors (e.g., WDR82, CPSF73) and transcription elongation factors (e.g., CDC73).
  • Inhibition of active transcription using DRB and triptolide.
  • Treatment of prostate cancer cells with adavosertib and JTE-607 (a CPSF73 inhibitor).
  • Assessment of DNA damage and cell viability.

Main Results:

  • Depleting transcription termination factors increased adavosertib-induced DNA damage during S-phase.
  • Inhibiting transcription or co-depleting CDC73 reduced adavosertib-induced DNA damage.
  • Combining adavosertib with JTE-607 synergistically reduced prostate cancer cell survival.
  • Elevated CPSF73 expression correlated with aggressive prostate cancer.

Conclusions:

  • Transcription termination is crucial for preventing DNA damage and cell death upon WEE1 inhibition.
  • Targeting transcription termination factors, such as CPSF73, in combination with WEE1 inhibitors shows promise for prostate cancer therapy.
  • Transcription termination safeguards against conflicts between transcription and replication during WEE1 inhibition.

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