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A chromosome-coupled ubiquitin-proteasome pathway is required for meiotic surveillance

Cell Death & Differentiation (2024)Cite this article

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Abstract

Defects in meiotic prophase can cause meiotic chromosome missegregation and aneuploid gamete formation. Meiotic checkpoints are activated in germ cells with meiotic defects, and cells with unfixed errors are eliminated by apoptosis. How such a surveillance process is regulated remains elusive. Here, we report that a chromosome-coupled ubiquitin-proteasome pathway (UPP) regulates meiotic checkpoint activation and promotes germ cell apoptosis in C. elegans meiosis-defective mutants. We identified an F-box protein, FBXL-2, that functions as a core component within the pathway. This chromosome-coupled UPP regulates meiotic DSB repair kinetics and chromosome dynamic behaviors in synapsis defective mutants. Disrupted UPP impairs the axial recruitment of the HORMA domain protein HIM-3, which is required for efficient germ cell apoptosis in synapsis defective mutants. Our data suggest that an efficient chromosome-coupled UPP functions as a part of the meiotic surveillance system by enhancing the integrity of the meiotic chromosome axis.

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Fig. 1: RPN-1 depletion causes altered meiotic progression kinetics and reduced germ cell apoptosis in synapsis defective mutants.
Fig. 2: Identification of meiotic chromosome-coupled UPP components.
Fig. 3: FBXL-2 promotes germ cell apoptosis in syp-1 and rad-51 mutant backgrounds.
Fig. 4: Chromosome-coupled UPP regulates DSB repair kinetics.
Fig. 5: FBXL-2 promotes chromosome dynamics in syp-1 mutant background.
Fig. 6: Chromosome-coupled UPP participates in meiotic surveillance by promoting axial loading of HIM-3.
Fig. 7: FBXL-2 recognizes chromatin-associated cohesin complexes.
Fig. 8: FBXL-2 interacts with proteasome components.

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All data generated or analyzed during this study are included in this published article and its Supplementary Information files.

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Acknowledgements

We thank Professor Monique Zetka (Department of Biology, McGill University) for the HTP-3 antibody. Some strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).

Funding

This work was supported by grants from the National Natural Science Foundation of China (32022018, 32370780, and 31871360) and the National Key R&D Program of China 2021YFA1101001.

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  1. These authors contributed equally: Ruirui Zhang, Bohan Liu.

Authors and Affiliations

  1. Center for Cell Structure and Function, College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Shandong Normal University, Jinan, 250358, China

    Ruirui Zhang, Bohan Liu, Yuqi Tian, Mingyu Xin, Xiuhua Huang, Yuanyuan Liu, Li Zhao, Feifei Qi, Ruoxi Wang, Xiaoqian Meng, Jun Zhou & Jinmin Gao

  2. State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, 300071, China

    Qian Li, Jun Zhou & Jinmin Gao

  3. Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing, 100871, China

    Jianguo Chen

  4. Center for Quantitative Biology, Peking University, Beijing, 100871, China

    Jianguo Chen

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Contributions

Conceptualization: JG and RZ; Methodology: JG and RZ; Investigation: RZ, BL, YT, MX, QL, XH, YL, LZ, FQ, RW, XM, and JG; Writing: JG, RZ, and JZ; Funding acquisition: JG and JZ; Resources: JG, JZ, and JC; Supervision: JG.

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Correspondence to Jinmin Gao.

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Zhang, R., Liu, B., Tian, Y. et al. A chromosome-coupled ubiquitin-proteasome pathway is required for meiotic surveillance. Cell Death Differ (2024). https://doi.org/10.1038/s41418-024-01375-6

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