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メ-Kleisin subunit of cohesin preserves the genome integrity of embryonic stem cells
Keun Pil Kim1,* (Professor), Seobin Yoon 1 (Graduate student), Eui-Hwan Choi1 (Research worker), Eui-Hwan Choi1,2 (Postdoctor), Eui-Hwan Choi1,2 (Postdoctor), Seo Jung Park1 (Graduate student), Seo Jung Park1 (Graduate Student)
1Department of Life Sciences, Chung-Ang University,
2New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation
Abstract
Cohesin is a ring-shaped protein complex that comprises the SMC1, SMC3, and メ-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 メ-kleisin factor RAD21 and meiosis-specific メ-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.
Abstract, Accepted Manuscript(in press) [Submitted on June 30, 2022, Accepted on December 22, 2022]
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