Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A
(2003) In Cancer Cell 3(3). p.247-258- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1126210
- author
- Sorensen, Claus Storgaard ; Syljuasen, Randi G ; Falck, Jacob ; Schroeder, Tine ; Rönnstrand, Lars LU ; Khanna, Kum Kum ; Zhou, Bin-Bing ; Bartek, Jiri and Lukas, Jiri
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer Cell
- volume
- 3
- issue
- 3
- pages
- 247 - 258
- publisher
- Cell Press
- external identifiers
-
- pmid:12676583
- scopus:0012966157
- ISSN
- 1878-3686
- DOI
- 10.1016/S1535-6108(03)00048-5
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- be9b0ba3-10c8-4034-b9a8-9ca686e4eedf (old id 1126210)
- date added to LUP
- 2016-04-01 12:15:16
- date last changed
- 2022-04-21 04:53:15
@article{be9b0ba3-10c8-4034-b9a8-9ca686e4eedf, 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 = {{Sorensen, Claus Storgaard and Syljuasen, Randi G and Falck, Jacob and Schroeder, Tine and Rönnstrand, Lars and Khanna, Kum Kum and Zhou, Bin-Bing and Bartek, Jiri and Lukas, Jiri}}, issn = {{1878-3686}}, language = {{eng}}, number = {{3}}, pages = {{247--258}}, publisher = {{Cell Press}}, series = {{Cancer Cell}}, title = {{Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A}}, url = {{http://dx.doi.org/10.1016/S1535-6108(03)00048-5}}, doi = {{10.1016/S1535-6108(03)00048-5}}, volume = {{3}}, year = {{2003}}, }