2. Academic Validation
  3. The ubiquitin-proteasome system regulates meiotic chromosome organization

The ubiquitin-proteasome system regulates meiotic chromosome organization

  • Proc Natl Acad Sci U S A. 2022 Apr 26;119(17):e2106902119. doi: 10.1073/pnas.2106902119.
Xiao Yang 1,  Meihui Song 2,  Ying Wang 2,  Taicong Tan 2,  Zhongyu Tian 1,  Binyuan Zhai 1,  Xuan Yang 1,  Yingjin Tan 1,  Yanding Cao 2,  Shaojun Dai 3,  Shunxin Wang 1 4 5 6,  Liangran Zhang 1 2 7 8
Affiliations

Affiliations

  • 1 Center for Reproductive Medicine, School of Medicine, Cheeloo College of Medicine, Shandong University, Shandong 250012, China.
  • 2 State Key Laboratory of Microbial Technology, Shandong University, Shandong 250012, China.
  • 3 Development Center of Plant Germplasm Resources, College of Life and Environmental Sciences, Shanghai Normal University, Shanghai 200234, China.
  • 4 National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Shandong 250012, China.
  • 5 Key Laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University, Shandong 250001, China.
  • 6 Shandong Provincial Clinical Research Center for Reproductive Health, Shandong University, Shandong 250012, China.
  • 7 Advanced Medical Research Institute, Shandong University, Shandong 250012, China.
  • 8 Key Laboratory of Animal Resistance Biology of Shandong Province, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Shandong 250014, China.
PMID: 35439061 DOI: 10.1073/pnas.2106902119
Abstract

Meiotic crossover (CO) recombination is tightly regulated by chromosome architecture to ensure faithful chromosome segregation and to reshuffle alleles between parental chromosomes for genetic diversity of progeny. However, regulation of the meiotic chromosome loop/axis organization is poorly understood. Here, we identify a molecular pathway for axis length regulation. We show that the cohesin regulator Pds5 can interact with proteasomes. Meiosis-specific depletion of proteasomes and/or Pds5 results in a similarly shortened chromosome axis, suggesting proteasomes and Pds5 regulate axis length in the same pathway. Protein ubiquitination is accumulated in pds5 and Proteasome mutants. Moreover, decreased chromosome axis length in these mutants can be largely rescued by decreasing ubiquitin availability and thus decreasing protein ubiquitination. Further investigation reveals that two ubiquitin E3 Ligases, SCF (Skp–Cullin–F-box) and Ufd4, are involved in this Pds5–ubiquitin/Proteasome pathway to cooperatively control chromosome axis length. These results support the hypothesis that ubiquitination of chromosome proteins results in a shortened chromosome axis, and cohesin–Pds5 recruits proteasomes onto chromosomes to regulate ubiquitination level and thus axis length. These findings reveal an unexpected role of the ubiquitin–proteasome system in meiosis and contribute to our knowledge of how Pds5 regulates meiotic chromosome organization. A conserved regulatory mechanism probably exists in higher eukaryotes.

Keywords

Pds5; chromosome axis; meiosis; proteasome; ubiquitin.

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