Related Experiment Video

Updated: May 27, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

Involvement of the nuclear proteasome activator PA28γ in the cellular response to DNA double-strand breaks

Adva Levy-Barda1, Yaniv Lerenthal, Anthony J Davis

  • 1The David and Inez Myers Laboratory for Cancer Genetics, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Cell Cycle (Georgetown, Tex.)
|December 3, 2011
PubMed

Insights

The nuclear proteasome activator PA28γ is a new player in the DNA damage response. Its depletion delays DNA double-strand break repair and disrupts repair pathway balance.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The DNA damage response (DDR) is crucial for maintaining genomic stability.
  • DNA double-strand breaks (DSBs) are highly cytotoxic lesions that trigger a vigorous DDR.
  • Proteasome-mediated protein degradation influences proteome dynamics after DNA damage.

Purpose of the Study:

  • To identify novel components of the DDR.
  • To investigate the role of the nuclear proteasome activator PA28γ (REGγ; PSME3) in DSB repair.
  • To elucidate the relationship between PA28γ, ATM kinase, and the proteasome in the DDR.

Main Methods:

  • Depletion of PA28γ using genetic approaches.
  • Assessment of cellular sensitivity to radiation (radiomimetic sensitivity).
  • Analysis of DSB repair kinetics and pathway choice (nonhomologous end-joining and homologous recombination).
  • Investigation of ATM-dependent phosphorylation and recruitment of PA28γ to DNA damage sites.
  • Monitoring proteasome accumulation at DNA damage sites.

Main Results:

  • PA28γ depletion causes sensitivity to DNA damaging agents and delays DSB repair.
  • PA28γ deficiency disrupts the balance between nonhomologous end-joining and homologous recombination repair pathways.
  • PA28γ is an ATM target, recruited to DNA damage sites.
  • PA28γ is essential for the rapid accumulation of proteasomes at DSB sites.

Conclusions:

  • PA28γ is a novel and essential component of the DNA damage response.
  • A new ATM-PA28γ-proteasome axis is identified, regulating timely DSB repair.
  • This axis plays a critical role in coordinating the cellular response to DNA double-strand breaks.

More Related Videos

Investigation of Protein Recruitment to DNA Lesions Using 405 Nm Laser Micro-irradiation12:29

Investigation of Protein Recruitment to DNA Lesions Using 405 Nm Laser Micro-irradiation

Published on: March 20, 2018

Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

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...
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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...
Homologous Recombination02:31

Homologous Recombination

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...