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Updated: Nov 10, 2025

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DNA topoisomerase 3 is required for efficient germ cell quality control

Maria Rosaria Dello Stritto1, Bernd Bauer1, Pierre Barraud2

  • 1Department of Chromosome Biology, Max Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.

The Journal of Cell Biology
|April 2, 2021
PubMed

Insights

Topoisomerase 3 depletion impairs germ cell quality control by blocking apoptosis. Restoring Bloom helicase activity in these mutants re-establishes apoptosis, revealing a novel role for topoisomerase 3 in DNA repair and cell fate.

Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • Meiosis involves quality control mechanisms to eliminate defective cells.
  • Oocyte elimination in Caenorhabditis elegans shares similarities with mammalian oocyte elimination.

Purpose of the Study:

  • To investigate the role of topoisomerase 3 in germ cell quality control.
  • To understand the molecular mechanisms underlying apoptosis resistance in topoisomerase 3-depleted cells.

Main Methods:

  • Depletion of topoisomerase 3 in Caenorhabditis elegans.
  • Analysis of DNA damage and apoptosis signaling pathways.
  • Genetic manipulation of DNA repair factors (CKU-70, CKU-80, POLQ-1, XPF-1) and the Bloom helicase-topoisomerase-RMI1 complex.

Main Results:

  • Topoisomerase 3 depletion leads to DNA lesions that resist p53 (cep-1)-dependent apoptosis.
  • Eliminating specific DNA repair factors alleviates the apoptosis block.
  • Depleting Bloom helicase in topoisomerase 3 mutants restores apoptosis.

Conclusions:

  • Topoisomerase 3 is essential for mounting an effective apoptotic response in germ cells.
  • Uncontrolled Bloom helicase activity may promote DNA repair pathways that inhibit apoptosis.
  • This study identifies a novel requirement for topoisomerase 3 in ensuring germ cell quality control.

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