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DNA Double Strand Breaks and Chromosomal Translocations Induced by DNA Topoisomerase II

Fernando Gómez-Herreros1,2

  • 1Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen del Rocío-CSIC-Universidad de Sevilla, Seville, Spain.

Frontiers in Molecular Biosciences
|January 11, 2020
PubMed

Insights

DNA double-strand breaks (DSBs) are critical DNA lesions. DNA topoisomerase II (TOP2) activity, especially during transcription, is increasingly linked to DSBs and chromosomal translocations, potentially driving cancer.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions.
  • DSBs can lead to mutations, chromosomal translocations, and cancer.
  • The mechanisms driving chromosomal translocation formation are not fully understood.

Purpose of the Study:

  • To summarize the origins of DNA topoisomerase II (TOP2)-induced DSBs.
  • To elucidate the factors influencing the translocation propensity of TOP2-associated breaks.
  • To highlight the role of TOP2 activity in genome instability and oncogenesis.

Main Methods:

  • Review of existing literature on DNA double-strand breaks.
  • Analysis of DNA topoisomerase II (TOP2) function and its relation to DNA damage.
  • Examination of transcription-associated TOP2 activity and its role in chromosomal rearrangements.

Main Results:

  • DNA topoisomerase II (TOP2) activity is a significant source of DNA double-strand breaks (DSBs).
  • Transcription-associated TOP2 activity is a major contributor to the formation of chromosomal translocations.
  • Specific origins and environments of TOP2-induced breaks influence their recombinogenic potential.

Conclusions:

  • DNA topoisomerase II (TOP2) activity is implicated in generating recombinogenic breaks.
  • Understanding TOP2-mediated DSBs is crucial for comprehending genome instability and cancer development.
  • Further research into TOP2 mechanisms can reveal new therapeutic targets for cancer treatment.
Keywords:
DNA topoisomerase IIDSB repairchromosomal translocationsgenome instabilitytranscription

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