Related Experiment Video
Updated: Jul 10, 2025
10:24
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
14.2K
p53 and p21 dynamics encode single-cell DNA damage levels, fine-tuning proliferation and shaping population
Nica Gutu1,2, Neha Binish1,3, Ulrich Keilholz1,4
1Charité Universitätsmedizin, Charité Comprehensive Cancer Center, Berlin, Germany.
Communications Biology
|November 24, 2023
Summary
Cells encode DNA damage levels to control proliferation. The p53-p21 network quantitatively adjusts proliferation rates by altering p53 signaling dynamics in response to DNA damage.
Area of Science:
- Cellular biology
- Molecular biology
- Systems biology
Background:
- Cellular checkpoints rapidly detect DNA damage for repair and proliferation control.
- Phenotypic variability arises from cellular stress and signaling noise, but its link to proliferation heterogeneity is unclear.
Purpose of the Study:
- Investigate how cells encode DNA damage levels to influence proliferation heterogeneity.
- Elucidate the role of the p53-p21 signaling network in this process.
Main Methods:
- Analysis of two single-cell datasets.
- Time-series analysis of p53 and p21 signaling dynamics.
- Examination of proliferation and signaling in equally irradiated cells.
Main Results:
- Cells encode heterogeneous DNA damage levels, shaping population-level proliferation.
- DNA damage strength is quantitatively translated into p53 and p21 signal parameters.
- Changes in p53 pulse periods drive cells out of low proliferative states.
Conclusions:
- The p53-p21 network plays a key role in quantitatively encoding DNA damage.
- This network fine-tunes cellular proliferation trajectories based on damage levels.
More Related Videos
Related Concept Videos
02:37DNA Damage can Stall the Cell Cycle
9.2K
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...
9.2K
02:23Abnormal Proliferation
4.5K
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...
4.5K
01:23Negative Regulator Molecules
35.4K
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.
35.4K
02:34Inhibition of Cdk Activity
4.8K
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...
4.8K
02:37DNA Damage Can Stall the Cell Cycle
2.6K
2.6K
01:27Molecular Factors Affecting Cell Division
3.1K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.1K