The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair

2005 ◽  
Vol 7 (2) ◽  
pp. 195-201 ◽  
Author(s):  
Claus Storgaard Sørensen ◽  
Lasse Tengbjerg Hansen ◽  
Jaroslaw Dziegielewski ◽  
Randi G. Syljuåsen ◽  
Cecilia Lundin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Homologous Recombination ◽  
Cell Cycle Checkpoint ◽  
Homologous Recombination Repair ◽  
Checkpoint Kinase ◽  
Recombination Repair ◽  
Cycle Checkpoint

scholarly journals Ethanol metabolism activates cell cycle checkpoint kinase, Chk2

Alcohol ◽  
2011 ◽  
Vol 45 (8) ◽  
pp. 785-793 ◽  
Author(s):  
Dahn L. Clemens ◽  
Katrina J. Mahan Schneider ◽  
Robert F. Nuss
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Checkpoint ◽  
Ethanol Metabolism ◽  
Checkpoint Kinase ◽  
Cycle Checkpoint

scholarly journals Inhibition of the ATR kinase enhances 5-FU sensitivity independently of nonhomologous end-joining and homologous recombination repair pathways

2020 ◽  
Vol 295 (37) ◽  
pp. 12946-12961
Author(s):  
Soichiro S. Ito ◽  
Yosuke Nakagawa ◽  
Masaya Matsubayashi ◽  
Yoshihiko M. Sakaguchi ◽  
Shinko Kobashigawa ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Mammalian Cells ◽  
Cell Cycle Checkpoint ◽  
Nonhomologous End Joining ◽  
Homologous Recombination Repair ◽  
Dna Breaks ◽  
End Joining ◽  
Nucleotide Synthesis ◽  
Recombination Repair ◽  
Repair Pathways

The anticancer agent 5-fluorouracil (5-FU) is cytotoxic and often used to treat various cancers. 5-FU is thought to inhibit the enzyme thymidylate synthase, which plays a role in nucleotide synthesis and has been found to induce single- and double-strand DNA breaks. ATR Ser/Thr kinase (ATR) is a principal kinase in the DNA damage response and is activated in response to UV– and chemotherapeutic drug–induced DNA replication stress, but its role in cellular responses to 5-FU is unclear. In this study, we examined the effect of ATR inhibition on 5-FU sensitivity of mammalian cells. Using immunoblotting, we found that 5-FU treatment dose-dependently induced the phosphorylation of ATR at the autophosphorylation site Thr-1989 and thereby activated its kinase. Administration of 5-FU with a specific ATR inhibitor remarkably decreased cell survival, compared with 5-FU treatment combined with other major DNA repair kinase inhibitors. Of note, the ATR inhibition enhanced induction of DNA double-strand breaks and apoptosis in 5-FU–treated cells. Using gene expression analysis, we found that 5-FU induced the activation of the intra-S cell-cycle checkpoint. Cells lacking BRCA2 were sensitive to 5-FU in the presence of ATR inhibitor. Moreover, ATR inhibition enhanced the efficacy of the 5-FU treatment, independently of the nonhomologous end-joining and homologous recombination repair pathways. These findings suggest that ATR could be a potential therapeutic target in 5-FU–based chemotherapy.

scholarly journals The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe

Oncogene ◽  
2004 ◽  
Vol 23 (25) ◽  
pp. 4353-4361 ◽  
Author(s):  
Maria Castedo ◽  
Jean-Luc Perfettini ◽  
Thomas Roumier ◽  
Kenichi Yakushijin ◽  
David Horne ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Checkpoint ◽  
Negative Regulator ◽  
Mitotic Catastrophe ◽  
Checkpoint Kinase ◽  
Cycle Checkpoint
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