α-Kleisin subunit of cohesin preserves the genome integrity of embryonic stem cells
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Cohesin is a ring-shaped protein complex that comprises theSMC1, SMC3, and α-kleisin proteins, STAG1/2/3 subunits, andauxiliary factors. Cohesin participates in chromatin remodeling,chromosome segregation, DNA replication, and gene expressionregulation during the cell cycle. Mitosis-specific α-kleisinfactor RAD21 and meiosis-specific α-kleisin factor REC8 are expressedin embryonic stem cells (ESCs) to maintain pluripotency. Here, we demonstrated that RAD21 and REC8 were involvedin maintaining genomic stability and modulating chromatinmodification in murine ESCs. When the kleisin subunits weredepleted, DNA repair genes were downregulated, thereby reducingcell viability and causing replication protein A (RPA) accumulation. This finding suggested that the repair of exposedsingle-stranded DNA was inefficient. Furthermore, the depletionof kleisin subunits induced DNA hypermethylation by upregulatingDNA methylation proteins. Thus, we proposed that thecohesin complex plays two distinct roles in chromatin remodelingand genomic integrity to ensure the maintenance of pluripotencyin ESCs.
Abstract
Cohesin is a ring-shaped protein complex that comprises theSMC1, SMC3, and α-kleisin proteins, STAG1/2/3 subunits, andauxiliary factors. Cohesin participates in chromatin remodeling,chromosome segregation, DNA replication, and gene expressionregulation during the cell cycle. Mitosis-specific α-kleisinfactor RAD21 and meiosis-specific α-kleisin factor REC8 are expressedin embryonic stem cells (ESCs) to maintain pluripotency. Here, we demonstrated that RAD21 and REC8 were involvedin maintaining genomic stability and modulating chromatinmodification in murine ESCs. When the kleisin subunits weredepleted, DNA repair genes were downregulated, thereby reducingcell viability and causing replication protein A (RPA) accumulation. This finding suggested that the repair of exposedsingle-stranded DNA was inefficient. Furthermore, the depletionof kleisin subunits induced DNA hypermethylation by upregulatingDNA methylation proteins. Thus, we proposed that thecohesin complex plays two distinct roles in chromatin remodelingand genomic integrity to ensure the maintenance of pluripotencyin ESCs.
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