RRC ID 77419
著者 Knoblochova L, Duricek T, Vaskovicova M, Zorzompokou C, Rayova D, Ferencova I, Baran V, Schultz RM, Hoffmann ER, Drutovic D.
タイトル CHK1-CDC25A-CDK1 regulate cell cycle progression and protect genome integrity in early mouse embryos.
ジャーナル EMBO Rep
Abstract 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.
巻・号 24(10)
ページ e56530
公開日 2023-10-9
DOI 10.15252/embr.202256530
PMID 37694680
PMC PMC10561370
IF 7.497
リソース情報
遺伝子材料 mCherry-hCdt1(1/100)Cy(-)/pcDNA3 (RDB15459)