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DNA topoisomerase 3 is required for efficient germ cell quality control

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 le...

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Autores principales: Dello Stritto, Maria Rosaria, Bauer, Bernd, Barraud, Pierre, Jantsch, Verena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025215/
https://www.ncbi.nlm.nih.gov/pubmed/33798260
http://dx.doi.org/10.1083/jcb.202012057
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author Dello Stritto, Maria Rosaria
Bauer, Bernd
Barraud, Pierre
Jantsch, Verena
author_facet Dello Stritto, Maria Rosaria
Bauer, Bernd
Barraud, Pierre
Jantsch, Verena
author_sort Dello Stritto, Maria Rosaria
collection PubMed
description 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 as-yet undescribed requirement for topoisomerase 3 in mounting an effective apoptotic response to ensure germ cell quality control.
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spelling pubmed-80252152021-05-04 DNA topoisomerase 3 is required for efficient germ cell quality control Dello Stritto, Maria Rosaria Bauer, Bernd Barraud, Pierre Jantsch, Verena J Cell Biol Article 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 as-yet undescribed requirement for topoisomerase 3 in mounting an effective apoptotic response to ensure germ cell quality control. Rockefeller University Press 2021-04-02 /pmc/articles/PMC8025215/ /pubmed/33798260 http://dx.doi.org/10.1083/jcb.202012057 Text en © 2021 Dello Stritto et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dello Stritto, Maria Rosaria
Bauer, Bernd
Barraud, Pierre
Jantsch, Verena
DNA topoisomerase 3 is required for efficient germ cell quality control
title DNA topoisomerase 3 is required for efficient germ cell quality control
title_full DNA topoisomerase 3 is required for efficient germ cell quality control
title_fullStr DNA topoisomerase 3 is required for efficient germ cell quality control
title_full_unstemmed DNA topoisomerase 3 is required for efficient germ cell quality control
title_short DNA topoisomerase 3 is required for efficient germ cell quality control
title_sort dna topoisomerase 3 is required for efficient germ cell quality control
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025215/
https://www.ncbi.nlm.nih.gov/pubmed/33798260
http://dx.doi.org/10.1083/jcb.202012057
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