Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein
- 14 January 1999
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 397 (6715), 172-175
- https://doi.org/10.1038/16488
Abstract
DNA damage activates a cell-cycle checkpoint that prevents mitosis while DNA repair is under way1. The protein Chk1 enforces this checkpoint by phosphorylating the mitotic inducer Cdc25 (2,3,4,5,6). Phosphorylation of Cdc25 by Chk1 creates a binding site in Cdc25 for 14-3-3 proteins5,6,7,8, but it is not known how 14-3-3 proteins regulate Cdc25. Rad24 is a 14-3-3 protein that is important in the DNA-damage checkpoint in fission yeast9. Here we show that Rad24 controls the intracellular distribution of Cdc25. Elimination of Rad24 causes nuclear accumulation of Cdc25. Activation of the DNA-damage checkpoint causes the net nuclear export of Cdc25 by a process that requires Chk1, Rad24 and nuclear-export machinery. Mutation of a putative nuclear-export signal in Rad24 impairs the nuclear exclusion of Rad24, the damage-induced nuclear export of Cdc25 and the damage checkpoint. Thus, Rad24 appears to function as an attachable nuclear-export signal that enhances the nuclear export of Cdc25 in response to DNA damage.Keywords
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