Related Experiment Video
Updated: Aug 8, 2025
07:55
Visualization of DNA Repair Proteins Interaction by Immunofluorescence
Published on: June 26, 2020
10.3K
The ATM-E6AP-MASTL axis mediates DNA damage checkpoint recovery
Yanqiu Li1, Feifei Wang1, Xin Li1
1Department of Oral Biology, University of Nebraska Medical Center, Lincoln, Nebraska, USA.
Biorxiv : the Preprint Server for Biology
|March 3, 2023
Summary
DNA damage triggers a temporary cell cycle arrest. This study reveals MASTL kinase upregulation initiates cell cycle recovery by inhibiting protein degradation, creating a timer for DNA damage checkpoint resolution.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- DNA damage activates checkpoints, causing transient cell cycle arrest via CDK suppression.
- Mechanisms initiating cell cycle recovery after DNA damage remain largely unknown.
Approach:
- Investigated MASTL kinase protein levels hours after DNA damage.
- Identified E3 ubiquitin ligase E6AP as responsible for MASTL degradation.
- Examined the role of ATM-mediated phosphorylation of E6AP in MASTL regulation.
Key Points:
- MASTL kinase is upregulated after DNA damage by decreased protein degradation.
- E6AP-mediated MASTL degradation is inhibited upon DNA damage due to E6AP/MASTL dissociation.
- ATM phosphorylates E6AP, promoting MASTL stabilization and cell cycle recovery.
Conclusions:
- ATM/ATR signaling activates the DNA damage checkpoint and initiates cell cycle recovery.
- This creates a timer-like mechanism ensuring the transient nature of the DNA damage checkpoint.
- MASTL kinase and E6AP play crucial roles in regulating DNA damage-induced cell cycle arrest and recovery.
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
02:19The Spindle Assembly Checkpoint
3.2K
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...
3.2K
02:37Restarting Stalled Replication Forks
5.9K
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,...
5.9K
02:31Homologous Recombination
50.8K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.8K
02:37DNA Damage Can Stall the Cell Cycle
2.6K
2.6K
01:20Mismatch Repair
5.0K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.0K