DNA topoisomerase 3 is required for efficient germ cell quality control.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
07 06 2021
07 06 2021
Historique:
received:
09
12
2020
revised:
21
02
2021
accepted:
12
03
2021
entrez:
2
4
2021
pubmed:
3
4
2021
medline:
12
10
2021
Statut:
ppublish
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 as-yet undescribed requirement for topoisomerase 3 in mounting an effective apoptotic response to ensure germ cell quality control.
Identifiants
pubmed: 33798260
pii: 211935
doi: 10.1083/jcb.202012057
pmc: PMC8025215
pii:
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Tumor Suppressor Protein p53
0
DNA Topoisomerases, Type I
EC 5.99.1.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Austrian Science Fund FWF
ID : P 31275
Pays : Austria
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
Informations de copyright
© 2021 Dello Stritto et al.
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