@article{193de150525011dd8d9f000ea68e967b,
title = "Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A.",
abstract = "Chk1 kinase coordinates cell cycle progression and preserves genome integrity. Here, we show that chemical or genetic ablation of human Chk1 triggered supraphysiological accumulation of the S phase-promoting Cdc25A phosphatase, prevented ionizing radiation (IR)-induced degradation of Cdc25A, and caused radioresistant DNA synthesis (RDS). The basal turnover of Cdc25A operating in unperturbed S phase required Chk1-dependent phosphorylation of serines 123, 178, 278, and 292. IR-induced acceleration of Cdc25A proteolysis correlated with increased phosphate incorporation into these residues generated by a combined action of Chk1 and Chk2 kinases. Finally, phosphorylation of Chk1 by ATM was required to fully accelerate the IR-induced degradation of Cdc25A. Our results provide evidence that the mammalian S phase checkpoint functions via amplification of physiologically operating, Chk1-dependent mechanisms.",
author = "S{\o}rensen, {Claus Storgaard} and Sylju{\aa}sen, {Randi G} and Jacob Falck and Tine Schroeder and Lars R{\"o}nnstrand and Khanna, {Kum Kum} and Bin-Bing Zhou and Jiri Bartek and Jiri Lukas",
note = "Keywords: Cell Cycle; Cell Cycle Proteins; DNA Replication; DNA-Binding Proteins; Enzyme Activation; Hela Cells; Humans; Kinetics; Models, Biological; Phosphorylation; Protein Kinases; Protein-Serine-Threonine Kinases; Radiation, Ionizing; S Phase; Serine; Signal Transduction; Tumor Cells, Cultured; Tumor Suppressor Proteins; cdc25 Phosphatases",
year = "2003",
language = "English",
volume = "3",
pages = "247--58",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}