Related Experiment Video

Updated: Jun 13, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

Proteolysis of Rad17 by Cdh1/APC regulates checkpoint termination and recovery from genotoxic stress

Liyong Zhang1, Chi-Hoon Park, Jing Wu

  • 1Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.

The EMBO Journal
|April 29, 2010
PubMed

Insights

The ubiquitin-proteasome system regulates DNA damage responses. Researchers found that Rad17 protein degradation by Cdh1/APC is crucial for ending checkpoint signaling and cell cycle recovery after DNA damage.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The ubiquitin-proteasome system (UPS) is vital for DNA damage response (DDR) and repair pathways.
  • Identifying novel UPS targets in DDR is crucial for understanding cellular stress responses.

Purpose of the Study:

  • To identify novel UPS targets within the DNA damage signaling network.
  • To investigate the role of Rad17 regulation by UPS in response to genotoxic stress.

Main Methods:

  • Utilized a non-biased assay to identify proteins with rapid turnover under genotoxic stress.
  • Characterized the regulation of Rad17 by the Cdh1/APC ubiquitin ligase complex.
  • Employed a degradation-resistant Rad17 mutant to assess checkpoint signaling dynamics.

Main Results:

  • Identified Rad17 as a protein upregulated and subsequently degraded following UV radiation exposure.
  • Demonstrated that UV-induced Rad17 oscillation is controlled by the Cdh1/APC ubiquitin ligase.
  • Showed that stabilized Rad17 inhibits checkpoint signaling termination and cell cycle re-entry.

Conclusions:

  • Proteolysis of Rad17 by Cdh1/APC is a key mechanism for terminating checkpoint signaling.
  • Rad17 degradation is essential for cellular recovery and progression from genotoxic stress.
  • This study elucidates a novel regulatory role for UPS in DNA damage response termination.

More Related Videos

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging06:44

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

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...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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, a...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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...