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Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein


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 (26). 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.

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Figure 1: Cdc25 nuclear staining is increased in late G2 and M phases.
Figure 2: Checkpoint-induced depletion of nuclear Cdc25.
Figure 3: Rad24 regulates Cdc25 localization.
Figure 4: Crm1 is required for nuclear export of Cdc25 and Rad24.
Figure 5: Analysis of rad24-nes mutants.


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We thank members of the cell-cycle labs at Scripps for support and encouragement, and M. Yanagida for crm1-809 cells. A.L.-G. was supported by the MEC, Spain. This work was supported by a grant from the NIH (to P.R.).

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Correspondence to Paul Russell.

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Lopez-Girona, A., Furnari, B., Mondesert, O. et al. Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein. Nature 397, 172–175 (1999).

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