BRISC and BRCA1-A complex member 2 () plays an essential role in promoting cell cycle progression and preventing cellular senescence. -deficient fibroblasts show proliferation defect and premature senescence compared with their wild-type (WT) counterpart. Pluripotent mouse embryonic stem cells (mESCs) are known to have unlimited cell proliferation and self-renewal capability without entering cellular senescence. Therefore, studying the role of in ESCs would enable us to understand the mechanism of in cellular aging, cell cycle regulation, and pluripotency in ESCs. For this study, we generated knockout () mESCs to investigate the function of in mESCs. We demonstrated that the loss of in mESCs leads to abnormal G1 phase retention in response to DNA damage induced by gamma irradiation or doxorubicin treatments. Key cell cycle regulators, CDC25A and CDK2, were found to be degraded in mESCs following gamma irradiation. In addition, mESCs expressed p53 strongly and significantly longer than in control mESCs, where p53 inhibited Nanog expression and G1/S cell cycle progression. The combined effects significantly reduced developmental pluripotency in mESCs. In summary, maintains cell cycle regulation and pluripotency in mESCs in response to induced DNA damage.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600899 | PMC |
http://dx.doi.org/10.3390/biomedicines8100397 | DOI Listing |
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