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Updated: Jun 26, 2025

Techniques to Induce and Quantify Cellular Senescence
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Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

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Transcription stress at telomeres leads to cytosolic DNA release and paracrine senescence

Athanasios Siametis1,2, Kalliopi Stratigi1, Despoina Giamaki1,2,3,4

  • 1Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece.

Nature Communications
|May 14, 2024
PubMed

Insights

Transcription stress causes DNA damage, leading to cellular senescence and aging. TFIIS-defective cells release telomeric DNA fragments via extracellular vesicles, triggering senescence in neighboring cells and promoting aging.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • Transcription stress is linked to DNA damage-driven aging, but the mechanism is unclear.
  • TFIIS (Transcription Factor II S) plays a crucial role in transcription elongation.

Purpose of the Study:

  • To elucidate the mechanism linking transcription stress to DNA damage and aging.
  • To investigate the role of TFIIS defects in cellular senescence and genome instability.

Main Methods:

  • Utilized Tcea1 knockout (Tcea1-/-) cells with a TFIIS defect.
  • Analyzed RNA Polymerase II (RNAPII) stalling, R-loop accumulation, telomere integrity, and chromatin structure.
  • Investigated the release of telomeric DNA fragments and their effect on neighboring cells.

Main Results:

  • Tcea1-/- cells exhibit RNAPII stalling at DNA damage sites, impaired transcription, and R-loop accumulation.
  • R-loops at telomeres contribute to telomeric DNA fragment release, triggering a viral-like immune response.
  • TFIIS-defective cells release extracellular vesicles containing telomeric DNA fragments, inducing senescence in recipient cells.

Conclusions:

  • Transcription stress, particularly TFIIS defects, leads to genome instability and cellular senescence.
  • Telomeric DNA fragments released via extracellular vesicles act as paracrine signals promoting aging.
  • This study reveals a novel mechanism by which transcription stress promotes aging through intercellular communication.

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