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Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A

Sorensen, Claus Storgaard ; Syljuasen, Randi G ; Falck, Jacob ; Schroeder, Tine ; Rönnstrand, Lars LU orcid ; Khanna, Kum Kum ; Zhou, Bin-Bing ; Bartek, Jiri and Lukas, Jiri (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)
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author
; ; ; ; ; ; ; and
publishing date
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}},
}