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Article Dans Une Revue Journal of Cell Biology Année : 2021

DNA topoisomerase 3 is required for efficient germ cell quality control

Maria Rosaria Dello Stritto
Bernd Bauer
Pierre Barraud
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Verena Jantsch
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Résumé

An important quality control mechanism eliminates meiocytes that have experienced recombination failure during meiosis. The culling of defective oocytes in Caenorhabditis elegans meiosis resembles late oocyte elimination in female mammals. Here we show that topoisomerase 3 depletion generates DNA lesions in both germline mitotic and meiotic compartments that are less capable of triggering p53 (cep-1)-dependent apoptosis, despite the activation of DNA damage and apoptosis signaling. Elimination of nonhomologous, alternative end joining and single strand annealing repair factors (CKU-70, CKU-80, POLQ-1, and XPF-1) can alleviate the apoptosis block. Remarkably, the ability of single mutants in the other members of the Bloom helicase-topoisomerase-RMI1 complex to elicit apoptosis is not compromised, and depletion of Bloom helicase in topoisomerase 3 mutants restores an effective apoptotic response. Therefore, uncontrolled Bloom helicase activity seems to direct DNA repair toward normally not used repair pathways, and this counteracts efficient apoptosis. This implicates an asyet undescribed requirement for topoisomerase 3 in mounting an effective apoptotic response to ensure germ cell quality control.
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Dates et versions

hal-03402250 , version 1 (25-10-2021)

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Maria Rosaria Dello Stritto, Bernd Bauer, Pierre Barraud, Verena Jantsch. DNA topoisomerase 3 is required for efficient germ cell quality control. Journal of Cell Biology, 2021, 220 (6), ⟨10.1083/jcb.202012057⟩. ⟨hal-03402250⟩
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