CHK1-CDC25A-CDK1 regulate cell cycle progression and protect genome integrity in early mouse embryos

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After fertilization, remodeling of the oocyte and sperm genomes is essential to convert these highly differentiated and transcriptionally quiescent cells into early cleavage-stage blastomeres that are transcriptionally active and totipotent. This developmental transition is accompanied by cell cycle adaptation, such as lengthening or shortening of the gap phases G1 and G2. However, regulation of these cell cycle changes is poorly understood, especially in mammals. Checkpoint kinase 1 (CHK1) is a protein kinase that regulates cell cycle progression in somatic cells. Here, we show that CHK1 regulates cell cycle progression in early mouse embryos by restraining CDK1 kinase activity due to CDC25A phosphatase degradation. CHK1 kinase also ensures the long G2 phase needed for genome activation and reprogramming gene expression in two-cell stage mouse embryos. Finally, Chk1 depletion leads to DNA damage and chromosome segregation errors that result in aneuploidy and infertility.
OriginalsprogEngelsk
Artikelnummere56530
TidsskriftEMBO Reports
Vol/bind24
Udgave nummer10
Antal sider22
ISSN1469-221X
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The authors dedicate this manuscript to the memory of Petr Solc, who directed the lab until his untimely death. D.D also thanks Jan Nevoral for the sperm samples, and Petr Svoboda and Jakub Cervenka for advice. D.D. was funded by grant #20-27742S from the Grant Agency of the Czech Republic. L.K. was supported by Ph.D. grant #1402217 from the Grant Agency of Charles University and Læge Sophus Carl Emil Friis og Hustru Olga Doris Friis' Legat. E.R.H. was supported by the European Research Council “ReCAP” (grant agreement 724718) and IRFD project 0134-00299B. V.B. was supported by grant VEGA 2/0072/19 from the Grant Agency of Slovakia.

Funding Information:
The authors dedicate this manuscript to the memory of Petr Solc, who directed the lab until his untimely death. D.D also thanks Jan Nevoral for the sperm samples, and Petr Svoboda and Jakub Cervenka for advice. D.D. was funded by grant #20‐27742S from the Grant Agency of the Czech Republic. L.K. was supported by Ph.D. grant #1402217 from the Grant Agency of Charles University and Læge Sophus Carl Emil Friis og Hustru Olga Doris Friis' Legat. E.R.H. was supported by the European Research Council “ReCAP” (grant agreement 724718) and IRFD project 0134‐00299B. V.B. was supported by grant VEGA 2/0072/19 from the Grant Agency of Slovakia.

Publisher Copyright:
© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

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