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Topoisomerase-mediated chromosomal break repair: an emerging player in many games

Mohamed E Ashour1, Reham Atteya2, Sherif F El-Khamisy1

  • 11] Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK. [2] Center for Genomics, Helmy Institute, Zewail City of Science and Technology, Giza 12588, Egypt.

Nature Reviews. Cancer
|February 20, 2015
PubMed

Insights

Protein-linked DNA breaks (PDBs) are crucial in cancer. This review explores how topoisomerases cause PDBs during transcription and their role in tissue-specific cancers, impacting therapy.

Area of Science:

  • Genomics
  • Molecular Biology
  • Cancer Research

Background:

  • Mammalian genomes face constant DNA and RNA damage.
  • Mechanisms of DNA/RNA integrity are known, but disorder pathology and tissue specificity remain unclear.
  • Protein-linked DNA breaks (PDBs) are significant endogenous DNA damage, implicated in cancer development and therapy.

Purpose of the Study:

  • To review mechanisms of topoisomerase-induced PDB formation and repair.
  • To focus on the role of PDBs during gene transcription.
  • To explore the link between PDBs and tissue-specific cancers.

Main Methods:

  • Literature review of DNA topoisomerase function.
  • Analysis of PDB formation and repair pathways.
  • Examination of PDBs in the context of gene transcription and cancer pathology.

Main Results:

  • DNA topoisomerases can induce PDBs through abortive activity.
  • PDBs play a role in gene transcription processes.
  • Topoisomerase-induced PDBs are linked to the development of tissue-specific cancers.

Conclusions:

  • Understanding PDB formation and repair is critical for cancer therapy.
  • The role of PDBs in gene transcription contributes to their pathological significance.
  • Targeting topoisomerase-induced PDBs may offer novel therapeutic strategies for specific cancers.

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