Cohesin variants and meiotic timing shape chromosome segregation accuracy

Yuanyuan Liu; Bohan Liu; Shuo Wang; Li Zhao; Qian Li; Feifei Qi; Ruoxi Wang; Jun Zhou; Jinmin Gao

doi:10.1016/j.jgg.2025.06.003

Cohesin variants and meiotic timing shape chromosome segregation accuracy

doi: 10.1016/j.jgg.2025.06.003

a. Center for Cell Structure and Function, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, Shandong Normal University, Jinan, Shandong 250014, China;
b. Department of Genetics and Cell Biology, State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University, Tianjin 300071, China

基金项目:

This work was supported by grants from the National Natural Science Foundation of China (32370780 and 32022018), the National Key Research and Development Program of China (2021YFA1101001), and the Taishan Scholars Program Special Fund. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).

详细信息

通讯作者:
Jinmin Gao,E-mail:jinmingao@sdnu.edu.cn

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出版历程
- 收稿日期: 2025-03-22
- 录用日期: 2025-06-22
- 修回日期: 2025-06-20
- 网络出版日期: 2025-07-11

Cohesin variants and meiotic timing shape chromosome segregation accuracy

a. Center for Cell Structure and Function, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, Shandong Normal University, Jinan, Shandong 250014, China;
b. Department of Genetics and Cell Biology, State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University, Tianjin 300071, China

Funds:

摘要

摘要:
The frequency of aneuploid gamete formation increases with maternal age, yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood. Using the multicellular organism Caenorhabditis elegans, we investigate the impact of mutations in the conserved cohesin complex on age-associated meiotic errors. Point mutations in the head domain of the cohesin component SMC-1, which alter local hydrophobicity, cause meiotic defects that vary with age. A severe mutation causes incomplete synapsis and defective crossover formation, and a minor one causes age-related diakinesis bivalent abnormalities. Notably, while the mild mutation causes defects only in aged worms, worms with the severe mutation exhibit significantly alleviated phenotypes with age. Genetic and cytological analyses suggest that this alleviation results from a slowed meiotic progression during early prophase, which restores impaired cohesin loading. These findings reveal that cohesin variants, meiotic progression speed during early prophase, and the overall duration of meiosis collectively shape the accuracy of meiotic chromosome segregation.
- Meiosis /
- Chromosome segregation /
- Cohesin /
- SMC-1 /
- Reproductive aging /
- Caenorhabditis elegans
Abstract:
The frequency of aneuploid gamete formation increases with maternal age, yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood. Using the multicellular organism Caenorhabditis elegans, we investigate the impact of mutations in the conserved cohesin complex on age-associated meiotic errors. Point mutations in the head domain of the cohesin component SMC-1, which alter local hydrophobicity, cause meiotic defects that vary with age. A severe mutation causes incomplete synapsis and defective crossover formation, and a minor one causes age-related diakinesis bivalent abnormalities. Notably, while the mild mutation causes defects only in aged worms, worms with the severe mutation exhibit significantly alleviated phenotypes with age. Genetic and cytological analyses suggest that this alleviation results from a slowed meiotic progression during early prophase, which restores impaired cohesin loading. These findings reveal that cohesin variants, meiotic progression speed during early prophase, and the overall duration of meiosis collectively shape the accuracy of meiotic chromosome segregation.
- Meiosis /
- Chromosome segregation /
- Cohesin /
- SMC-1 /
- Reproductive aging /
- Caenorhabditis elegans