Association of Chk1 with 14-3-3 proteins is stimulated by DNA damage

Lin Chen, Ting Hsiu Liu, Nancy C. Walworth

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)675-685
Number of pages11
JournalGenes and Development
Volume13
Issue number6
DOIs
StatePublished - Mar 15 1999

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Keywords

  • 14-3-3 protein
  • Cdc25
  • Cell cycle
  • Checkpoint
  • Chk1
  • DNA damage

Fingerprint

Dive into the research topics of 'Association of Chk1 with 14-3-3 proteins is stimulated by DNA damage'. Together they form a unique fingerprint.

Cite this