Knoblochova Lucie, Duricek Tomas, Vaskovicova Michaela, Zorzompokou Chrysoula, Rayova Diana, Ferencova Ivana, Baran Vladimir, Schultz Richard M, Hoffmann Eva R, Drutovic David
Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Libechov, Czech Republic.
Faculty of Science, Charles University, Prague, Czech Republic.
EMBO Rep. 2023 Oct 9;24(10):e56530. doi: 10.15252/embr.202256530. Epub 2023 Sep 11.
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.
受精后，卵母细胞和精子基因组的重塑对于将这些高度分化且转录静止的细胞转化为转录活跃且具有全能性的早期卵裂期卵裂球至关重要。这种发育转变伴随着细胞周期的适应性变化，例如G1期和G2期的延长或缩短。然而，这些细胞周期变化的调控机制尚不清楚，尤其是在哺乳动物中。检查点激酶1（CHK1）是一种调节体细胞细胞周期进程的蛋白激酶。在此，我们表明CHK1通过因CDC25A磷酸酶降解而抑制CDK1激酶活性来调节小鼠早期胚胎的细胞周期进程。CHK1激酶还确保了二细胞期小鼠胚胎基因组激活和重编程基因表达所需的长G2期。最后，Chk1缺失会导致DNA损伤和染色体分离错误，从而导致非整倍体和不育。
