Related Experiment Video

Updated: Jun 24, 2026

Laser Micro-Irradiation to Study DNA Recruitment During S Phase
07:11

Laser Micro-Irradiation to Study DNA Recruitment During S Phase

Published on: April 16, 2021

Involvement of Exo1b in DNA damage-induced apoptosis

Emma Bolderson1, Derek J Richard, Winfried Edelmann

  • 1Signal Transduction Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.

Nucleic Acids Research
|April 3, 2009
PubMed

Insights

The DNA repair enzyme Exonuclease 1 (Exo1) plays a crucial role in initiating apoptosis following DNA damage. Its cleavage by caspase-3 during this process may help prevent DNA repair, ensuring cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Apoptosis is vital for maintaining genomic integrity.
  • Cell survival mechanisms, including DNA repair, are suppressed during DNA damage-induced apoptosis.

Purpose of the Study:

  • To investigate the role of mammalian DNA repair enzyme Exonuclease 1 (Exo1) in DNA damage-induced apoptosis.
  • To elucidate the mechanism by which Exo1 influences apoptosis progression and its regulation.

Main Methods:

  • Depletion of Exo1 in human and mouse embryonic fibroblasts.
  • Assays to determine Exo1's position in the apoptotic pathway (caspase-3 activation, DNA fragmentation, cytochrome c release).
  • Analysis of Exo1 cleavage by caspase-3, including mapping the cleavage site and using a cleavage-resistant mutant.

Main Results:

  • Exo1 depletion delayed DNA damage-induced apoptosis.
  • Exo1 acts upstream of caspase-3 activation, DNA fragmentation, and cytochrome c release.
  • Exo1 is cleaved by caspase-3 at Asp514 during apoptosis, generating a specific fragment.

Conclusions:

  • Exo1 is essential for the timely induction of apoptosis after DNA damage.
  • Caspase-3 mediated cleavage and degradation of Exo1 occur during apoptosis.
  • This cleavage may serve to inhibit DNA repair, facilitating programmed cell death.

More Related Videos

Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

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

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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
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...