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Transcription in check at DNA double-strand breaks

Lea Pradel1, Aline Marnef1, Gaelle Legube1

  • 1CBI (Centre de Biologie Intégrative), University of Toulouse, CNRS, Toulouse, France.

Trends in Genetics : TIG
|July 10, 2026
PubMed

Insights

Cells coordinate DNA repair with transcription to prevent interference. This review explores how stalled RNA polymerase II at DNA breaks may produce unique RNAs, reconciling conflicting findings.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA double-strand breaks (DSBs) in transcribed regions require coordination between transcription and repair.
  • Signaling pathways repress transcription via chromatin remodeling and RNA polymerase II (RNAPII) modification.
  • Mechanisms integrating transcription and DNA repair remain unclear.

Purpose of the Study:

  • To review recent advances in coordinating transcription and DNA repair at DSBs.
  • To compare DSB repair with pathways for transcription-blocking lesions.
  • To propose a model involving altered transcription cycles at DSBs.

Main Methods:

  • Literature review of recent advances in DNA repair and transcription regulation.
  • Comparative analysis of DSB repair pathways and transcription-blocking lesion responses.
  • Discussion of potential mechanisms for reconciling conflicting observations.

Main Results:

  • Signaling cascades initiate transcription repression at DSBs.
  • Parallels exist between DSB repair and pathways for UV or DNA-protein crosslink lesions.
  • Altered transcription cycles, including stalled RNAPII, may occur at DSB sites.

Conclusions:

  • Tightly coordinated transcription and DNA repair are essential at DSBs.
  • Stalled RNAPII at DSBs might generate distinct RNA species.
  • This model offers a unified explanation for previous observations.

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