Related Experiment Video
Updated: Jun 29, 2025
13:10
Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
Published on: June 9, 2017
10.0K
REV7-p53 interaction inhibits ATM-mediated DNA damage signaling
Megan Biller1, Sara Kabir1, Chkylle Boado1
1Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA.
Cell Cycle (Georgetown, Tex.)
|April 1, 2024
Summary
REV7 protein directly binds to p53, inhibiting its phosphorylation and promoting its destabilization. This reveals a new role for REV7 in DNA damage response signaling and genome stability.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- REV7 is a known regulator of cell cycle and DNA repair pathways like Trans-Lesion Synthesis (TLS) and Fanconi Anemia (FA).
- A direct role for REV7 in the DNA damage response (DDR) signaling pathway remained uncharacterized.
Purpose of the Study:
- To investigate the novel function of REV7 in DNA Double-Strand Break (DSB)-induced p53 signaling.
- To elucidate the mechanism by which REV7 influences p53 activity and stability.
Main Methods:
- Co-immunoprecipitation assays to demonstrate direct binding of REV7 to p53.
- Western blotting to assess p53 phosphorylation and stability.
- Cellular assays to evaluate the impact of REV7 on DSB-induced signaling.
Main Results:
- REV7 directly binds to the p53 protein.
- REV7 inhibits ATM-dependent phosphorylation of p53 at Ser15.
- REV7 contributes to the destabilization of p53.
Conclusions:
- REV7 plays a critical role in integrating multiple cellular processes, including cell cycle regulation and DNA repair.
- REV7's novel function in DSB-induced p53 signaling impacts cell viability and genome stability.
- REV7 acts as a key modulator of the DNA damage response pathway.
Related Concept Videos
02:37DNA Damage can Stall the Cell Cycle
9.1K
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...
9.1K
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
01:31The Intrinsic Apoptotic Pathway
6.5K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
01:19Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
02:37Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K