Reference - Detail
| RRC ID | 75939 |
|---|---|
| Author | Dello Stritto MR, Bauer B, Barraud P, Jantsch V. |
| Title | DNA topoisomerase 3 is required for efficient germ cell quality control. |
| Journal | J Cell Biol |
| Abstract |
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. |
| Volume | 220(6) |
| Published | 2021-6-7 |
| DOI | 10.1083/jcb.202012057 |
| PII | 211935 |
| PMID | 33798260 |
| PMC | PMC8025215 |
| MeSH | Animals Apoptosis Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA Damage DNA Repair DNA Topoisomerases, Type I / genetics DNA Topoisomerases, Type I / metabolism* Germ Cells / cytology* Germ Cells / metabolism Meiosis* Oocytes / cytology Oocytes / metabolism Quality Control* Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 30 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1298 tm1145 tm1937 tm1524 tm2842 |