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Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms.

In response to DNA damage, cells activate checkpoint pathways that prevent cell cycle progression. In fission yeast and mammals, mitotic arrest in response to DNA damage requires inhibitory Cdk phosphorylation regulated by Chk1. This study indicates that Chk1 is required for function of the DNA damage checkpoint in Saccharomyces cerevisiae but acts through a distinct mechanism maintaining the abundance of Pds1, an anaphase inhibitor. Unlike other checkpoint mutants, chk1 mutants were only mildly sensitive to DNA damage, indicating that checkpoint functions besides cell cycle arrest influence damage sensitivity. Another kinase, Rad53, was required to both maintain active cyclin-dependent kinase 1, Cdk1(Cdc28), and prevent anaphase entry after checkpoint activation. Evidence suggests that Rad53 exerts its role in checkpoint control through regulation of the Polo kinase Cdc5. These results support a model in which Chk1 and Rad53 function in parallel through Pds1 and Cdc5, respectively, to prevent anaphase entry and mitotic exit after DNA damage. This model provides a possible explanation for the role of Cdc5 in DNA damage checkpoint adaptation.

Pubmed ID: 10550056


  • Sanchez Y
  • Bachant J
  • Wang H
  • Hu F
  • Liu D
  • Tetzlaff M
  • Elledge SJ


Science (New York, N.Y.)

Publication Data

November 5, 1999

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM44664

Mesh Terms

  • Anaphase
  • Anaphase-Promoting Complex-Cyclosome
  • CDC2 Protein Kinase
  • Cell Cycle Proteins
  • Checkpoint Kinase 2
  • Cyclin B
  • DNA Damage
  • DNA, Fungal
  • Fungal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligases
  • Mitosis
  • Mutation
  • Nuclear Proteins
  • Phosphorylation
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • S Phase
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Securin
  • Ubiquitin-Protein Ligase Complexes
  • Ubiquitin-Protein Ligases