Related Experiment Videos
Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase
B Furnari1, N Rhind, P Russell
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science (New York, N.Y.)
|September 5, 1997
Summary
DNA damage triggers cell cycle arrest at the G2 checkpoint. This study identifies Cdc25 phosphatase, not Wee1 kinase, as a key target of the Chk1 kinase in the DNA damage response pathway.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- DNA damage induces cell cycle arrest at the G2 checkpoint.
- This arrest requires inhibitory phosphorylation of the kinase Cdc2.
- The kinases Wee1 and Cdc25 regulate Cdc2 phosphorylation and are critical for checkpoint control.
Purpose of the Study:
- To investigate whether Wee1 and Cdc25 are targets of the essential checkpoint kinase, Chk1.
- To elucidate the role of Chk1 in regulating Cdc2 phosphorylation during the DNA damage response.
Main Methods:
- Utilized fission yeast mutants (cdc2-3w Deltacdc25) expressing activated Cdc2 and lacking Cdc25.
- Assessed cellular responses to Wee1, Chk1, and irradiation in these mutants.
- Investigated in vivo association and phosphorylation of Cdc25 with Chk1.
Main Results:
- Fission yeast cells lacking Cdc25 were responsive to Wee1 but not Chk1 or irradiation.
- Overexpression of Chk1 mimicked the phenotype of Cdc25 loss.
- Cdc25 was found to associate with Chk1 in vivo and undergo phosphorylation within Chk1 complexes.
Conclusions:
- Cdc25 phosphatase is a direct target of the Chk1 kinase in the DNA damage checkpoint pathway.
- Wee1 kinase is not a direct target of Chk1 in this context.
- These findings clarify the regulatory mechanism of the G2/M DNA damage checkpoint.