Association of Chk1 with 14-3-3 proteins is stimulated by DNA damage
- Department of Pharmacology, University of Medicine and Dentistry of New Jersey (UMDNJ)–Robert Wood Johnson Medical School, Joint Graduate Program in Biochemistry, UMDNJ and Rutgers University, Graduate Program in Microbiology and Molecular Genetics, Rutgers University, and The Cancer Institute of New Jersey, Piscataway, New Jersey 08854 USA
Abstract
The protein kinase Chk1 is required for cell cycle arrest in response to DNA damage. We have found that the 14-3-3 proteins Rad24 and Rad25 physically interact with Chk1 in fission yeast. Association of Chk1 with 14-3-3 proteins is stimulated in response to DNA damage. DNA damage results in phosphorylation of Chk1 and the 14-3-3 proteins bind preferentially to the phosphorylated form. Genetic analysis has independently implicated both Rad24 and Rad25 in the DNA-damage checkpoint pathway. We suggest that DNA damage-dependent association of phosphorylated Chk1 with 14-3-3 proteins mediates an important step along the DNA-damage checkpoint pathway, perhaps by directing Chk1 to a particular substrate or to a particular location within the cell. An additional role for 14-3-3 proteins in the DNA-damage checkpoint has been suggested based on the observation that human Chk1 can phosphorylate Cdc25C in vitro creating a 14-3-3 binding site. Our results suggest that in fission yeast the interaction between the 14-3-3 proteins and Cdc25 does not require Chk1 function and is unaffected by DNA damage, in sharp contrast to the interaction between the 14-3-3 proteins and Chk1.
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↵Corresponding author.
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E-MAIL walworna{at}umdnj.edu; FAX (732) 235-4073.
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- Received November 19, 1998.
- Accepted February 3, 1999.
- Cold Spring Harbor Laboratory Press
