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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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α-Kleisin subunit of cohesin preserves the genome integrity of embryonic stem cells

  • Seobin Yoon (Department of Life Sciences, Chung-Ang University) ;
  • Eui-Hwan Choi (Department of Life Sciences, Chung-Ang University) ;
  • Seo Jung Park (Department of Life Sciences, Chung-Ang University) ;
  • Keun Pil Kim (Department of Life Sciences, Chung-Ang University)
  • Received : 2022.06.30
  • Accepted : 2022.12.22
  • Published : 2023.02.28
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Abstract

Cohesin is a ring-shaped protein complex that comprises the SMC1, SMC3, and α-kleisin proteins, STAG1/2/3 subunits, and auxiliary factors. Cohesin participates in chromatin remodeling, chromosome segregation, DNA replication, and gene expression regulation during the cell cycle. Mitosis-specific α-kleisin factor RAD21 and meiosis-specific α-kleisin factor REC8 are expressed in embryonic stem cells (ESCs) to maintain pluripotency. Here, we demonstrated that RAD21 and REC8 were involved in maintaining genomic stability and modulating chromatin modification in murine ESCs. When the kleisin subunits were depleted, DNA repair genes were downregulated, thereby reducing cell viability and causing replication protein A (RPA) accumulation. This finding suggested that the repair of exposed single-stranded DNA was inefficient. Furthermore, the depletion of kleisin subunits induced DNA hypermethylation by upregulating DNA methylation proteins. Thus, we proposed that the cohesin complex plays two distinct roles in chromatin remodeling and genomic integrity to ensure the maintenance of pluripotency in ESCs.

Keywords

Acknowledgement

We thank Soojin Lee of Chung-Ang University for helping in the preparation of the REC8 plasmid. This work was supported by grants to K.P.K. from the National Research Foundation of Korea, funded by the Ministry of Science, ICT, & Future Planning (No. 2020R1A2C2011887).

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