Related Experiment Video

Updated: Oct 8, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Cdc25-dependent activation of cyclin A/cdk2 is blocked in G2 phase arrested cells independently of ATM/ATR

S Goldstone1, S Pavey, A Forrest

  • 1Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, and Joint Experimental Oncology Program, Department of Pathology, University of Queensland, Brisbane, QLD, Australia.

Oncogene
|April 21, 2001
PubMed

Insights

Cyclin A/cdk2 activity during G2 phase is regulated by cdc25. DNA damage blocks this activation, suggesting a role in the G2 checkpoint control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cyclin A/cdk2 plays a role in cell cycle regulation.
  • Its function and regulation during the G2 phase remain unclear.

Purpose of the Study:

  • To investigate the regulation of cyclin A/cdk2 activity during normal G2 phase progression.
  • To understand its role in genotoxin-induced G2 arrest.

Main Methods:

  • Examined cyclin A/cdk2 activity during G2 phase.
  • Studied G2 arrest induced by DNA damage.
  • Assessed the role of cdc25 isoforms (cdc25B, cdc25C) and ATM/ATR signaling.

Main Results:

  • Cyclin A/cdk2 is activated in early G2 by cdc25.
  • DNA damage-induced G2 arrest blocks cdc25-dependent activation of cyclin A/cdk2 and cyclin B1/cdc2.
  • Ectopic expression of cdc25B, not cdc25C, reactivates both cyclin complexes.
  • The block in activation is independent of ATM/ATR signaling.

Conclusions:

  • The G2 checkpoint prevents cyclin A/cdk2 activation in a manner independent of ATM/ATR.
  • This ATM/ATR-independent block may represent an additional layer of checkpoint control.
  • Inhibition of G2 phase cyclin A/cdk2 activation contributes to the G2 checkpoint arrest.

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 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...
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...
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...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.