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

0576852 - ÚŽFG 2024 RIV US eng J - Journal Article
Knoblochová, Lucie - Ďuríček, Tomáš - Vaškovičová, Michaela - Zorzompokou, Chrysoula - Rayová, Diana - Ferencová, Ivana - Baran, V. - Schultz, R. M. - Hoffmann, E. R. - Drutovič, Dávid
CHK1-CDC25A-CDK1 regulate cell cycle progression and protect genome integrity in early mouse embryos.
Embo Reports. Roč. 24, č. 10 (2023), č. článku e56530. ISSN 1469-221X. E-ISSN 1469-3178
R&D Projects: GA ČR(CZ) GA20-27742S
Institutional support: RVO:67985904
Keywords : CDC25A phosphatase * CDK1 kinase * cell cycle regulation * CHK1 kinase * early mouse embryos
OECD category: Developmental biology
Impact factor: 7.7, year: 2022
Method of publishing: Open access
https://www.embopress.org/doi/full/10.15252/embr.202256530

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.
Permanent Link: https://hdl.handle.net/11104/0346247