Related Experiment Video

Updated: Sep 26, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

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
PubMed

Insights

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.

More Related Videos

Study of the DNA Damage Checkpoint using Xenopus Egg Extracts10:55

Study of the DNA Damage Checkpoint using Xenopus Egg Extracts

Published on: November 5, 2012

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...