Related Experiment Video
Updated: May 15, 2026
10:55
Study of the DNA Damage Checkpoint using Xenopus Egg Extracts
Published on: November 5, 2012
A predictive mathematical model of the DNA damage G2 checkpoint
Kevin J Kesseler1, Michael L Blinov, Timothy C Elston
1Department of Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, NC 27599-7255, USA.
Journal of Theoretical Biology
|December 26, 2012
Summary
This study models the cell cycle's G2 to mitosis transition, revealing how DNA damage impacts it. Mathematical modeling predicts how protein changes affect cell cycle progression and DNA damage response.
Area of Science:
- Cell Biology
- Systems Biology
- Mathematical Modeling
Background:
- The G2 to M phase transition is crucial for cell cycle progression.
- DNA damage triggers a G2 checkpoint to prevent cell division with compromised DNA.
- Understanding the regulatory network of G2/M transition is vital for cancer research.
Purpose of the Study:
- To construct a predictive mathematical model of the G2 to M cell cycle transition.
- To simulate the effects of DNA damage on G2/M regulation.
- To investigate the impact of protein perturbations on cell cycle progression and DNA damage response.
Main Methods:
- Developed a rule-based mathematical model using BioNetGen software.
- Simulated protein interactions, nuclear-cytoplasmic transport, and phospho-epitope dynamics.
- Analyzed effects of protein depletion or overexpression in the presence and absence of DNA damage.
Main Results:
- Model accurately recapitulates DNA damage-induced G2 delay.
- Plk1 depletion delayed mitotic entry and recovery from G2 arrest.
- MPF overexpression attenuated DNA damage-induced G2 delay.
- Predicted a novel state where pkMyt1 depletion causes accumulation of inactive MPF in G2 cells with DNA damage.
Conclusions:
- The model provides insights into G2/M transition regulation and DNA damage response.
- It can predict cell cycle behavior under various genetic and damage conditions.
- This predictive model may aid in understanding cancer progression and therapy sensitivity.
Related Concept Videos
02:36DNA 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...
02:36DNA 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...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
01:28The Cell Cycle Control System
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
02:11The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
02:19The 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...
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...