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Transcription-associated DNA breaks and cancer: A matter of DNA topology

Agnese Cristini1, Mathéa Géraud1, Olivier Sordet1

  • 1Cancer Research Center of Toulouse, INSERM, Université de Toulouse, Université Toulouse III Paul Sabatier, CNRS, Toulouse, France.

International Review of Cell and Molecular Biology
|September 11, 2021
PubMed

Insights

Transcription can cause DNA breaks, threatening genome integrity and leading to cancer. Deregulated topoisomerase activity exacerbates this, promoting DNA breaks and R-loops, which are linked to cancer development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Biology

Background:

  • Transcription is vital but poses risks to genome integrity.
  • Transcription-associated DNA breaks can lead to mutations and cancer.
  • These breaks often stem from topological stress during transcription.

Purpose of the Study:

  • To review the role of transcription in DNA break formation.
  • To discuss how topoisomerase deregulation impacts transcription and DNA breaks.
  • To explore the connection between these processes and cancer.

Main Methods:

  • Literature review of transcription-associated DNA damage.
  • Analysis of topoisomerase function and its role in genome instability.
  • Examination of R-loop formation and its contribution to DNA breaks.

Main Results:

  • Transcription-associated DNA breaks arise from topological problems.
  • Impaired removal of torsional stress promotes R-loops and DNA breaks.
  • Topoisomerases, while relaxing DNA, can introduce breaks; their stabilization is oncogenic.

Conclusions:

  • Transcription is a source of DNA breaks, impacting genome stability.
  • Topoisomerase activity deregulation is linked to increased DNA breaks, R-loops, and cancer.
  • Understanding these mechanisms is crucial for cancer research and therapy.
Keywords:
CancerDNA breakDNA topologyGenome instabilityOncogenic translocationR-loopRNA polymeraseRNA/DNA hybridTopoisomeraseTranscription

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