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

Nature. 1999 Jan 14;397(6715):172-5. doi: 10.1038/16488.

Abstract

DNA damage activates a cell-cycle checkpoint that prevents mitosis while DNA repair is under way. The protein Chk1 enforces this checkpoint by phosphorylating the mitotic inducer Cdc25. Phosphorylation of Cdc25 by Chk1 creates a binding site in Cdc25 for 14-3-3 proteins, 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 yeast. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • Biological Transport
  • CDC2 Protein Kinase / metabolism
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus / metabolism*
  • DNA Damage*
  • Exportin 1 Protein
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins
  • Karyopherins*
  • Mutagenesis
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Proteins / physiology*
  • Receptors, Cytoplasmic and Nuclear*
  • Recombinant Fusion Proteins / genetics
  • Schizosaccharomyces / physiology
  • Schizosaccharomyces / radiation effects
  • Schizosaccharomyces pombe Proteins
  • Tyrosine 3-Monooxygenase*
  • Ultraviolet Rays
  • ras-GRF1*

Substances

  • 14-3-3 Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Fungal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Karyopherins
  • Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Schizosaccharomyces pombe Proteins
  • rad24 protein, S pombe
  • ras-GRF1
  • Tyrosine 3-Monooxygenase
  • CDC2 Protein Kinase
  • Phosphoprotein Phosphatases