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XB-ART-14234
J Cell Biol September 21, 1998; 142 (6): 1559-69.
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The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.

Kumagai A , Guo Z , Emami KH , Wang SX , Dunphy WG .


Abstract
We have analyzed the role of the protein kinase Chk1 in checkpoint control by using cell-free extracts from Xenopus eggs. Recombinant Xenopus Chk1 (Xchk1) phosphorylates the mitotic inducer Cdc25 in vitro on multiple sites including Ser-287. The Xchk1-catalyzed phosphorylation of Cdc25 on Ser-287 is sufficient to confer the binding of 14-3-3 proteins. Egg extracts from which Xchk1 has been removed by immunodepletion are strongly but not totally compromised in their ability to undergo a cell cycle delay in response to the presence of unreplicated DNA. Cdc25 in Xchk1-depleted extracts remains bound to 14-3-3 due to the action of a distinct Ser-287-specific kinase in addition to Xchk1. Xchk1 is highly phosphorylated in the presence of unreplicated or damaged DNA, and this phosphorylation is abolished by caffeine, an agent which attenuates checkpoint control. The checkpoint response to unreplicated DNA in this system involves both caffeine-sensitive and caffeine-insensitive steps. Our results indicate that caffeine disrupts the checkpoint pathway containing Xchk1.

PubMed ID: 9744884
PMC ID: PMC2141764
Article link: J Cell Biol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: chek1 neb ptpa rasgrf1


Article Images: [+] show captions
References [+] :
Bentley, The Schizosaccharomyces pombe rad3 checkpoint gene. 1997, Pubmed