Related Experiment Video

Updated: Jul 16, 2026

Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice
17:59

Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice

Published on: April 3, 2011

Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia mutated (ATM)-mediated cell cycle arrest

Weidong Yong1, Shideng Bao, Hanying Chen

  • 1Herman B Wells Center for Pediatric Research, Section of Pediatric Cardiology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

The Journal of Biological Chemistry
|March 23, 2007
PubMed

Insights

Protein phosphatase 5 (Ppp5) is crucial for the G(2)/M DNA damage checkpoint. Ppp5 deficiency impairs the ATM-mediated signaling pathway, affecting DNA repair and cell cycle regulation after ionizing radiation exposure.

Area of Science:

  • Cellular biology
  • Molecular genetics
  • DNA damage response

Background:

  • Protein phosphatase 5 (Ppp5) is a tetratricopeptide repeat domain protein involved in various cellular processes.
  • Its specific role in cell cycle checkpoint regulation, particularly in response to DNA damage, remains unclear.

Purpose of the Study:

  • To investigate the physiological function of Ppp5 in cell cycle checkpoint regulation.
  • To determine Ppp5's role in the ATM/ATR signaling pathway following DNA damage.

Main Methods:

  • Generation of Ppp5-deficient mice and isolation of mouse embryonic fibroblast (MEF) cells.
  • Assessment of replication and G(2)/M DNA damage checkpoints using hydroxyurea and ionizing radiation (IR).
  • Measurement of ATM kinase activity and its downstream substrates (Rad17, Chk2) in response to IR.

Main Results:

  • Ppp5-deficient mice and MEF cells are viable and maintain normal replication checkpoints.
  • Ppp5-deficient MEF cells exhibit a significant defect in the G(2)/M DNA damage checkpoint after IR exposure.
  • IR-induced ATM kinase activity, Rad17 and Chk2 phosphorylation, and Rad17 nuclear foci formation are attenuated in Ppp5-deficient MEFs.

Conclusions:

  • Ppp5 plays a critical role in activating the ATM-mediated G(2)/M DNA damage checkpoint pathway.
  • Ppp5 directly regulates ATM signaling activation in response to DNA damage in vivo.

More Related Videos

Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures08:41

Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures

Published on: December 27, 2024

Strategies for Assessing Autistic-Like Behaviors in Mice07:38

Strategies for Assessing Autistic-Like Behaviors in Mice

Published on: September 20, 2024

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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
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...
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...