Related Experiment Video

Updated: Jul 8, 2026

Visualization and Quantitative Analysis of Genotoxin-Induced PARP1/PARP2 Activation in Cells Using a Fluorescent Fusion Protein-Based Reporter
07:53

Visualization and Quantitative Analysis of Genotoxin-Induced PARP1/PARP2 Activation in Cells Using a Fluorescent Fusion Protein-Based Reporter

Published on: April 17, 2026

The roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death

O Cohausz1, C Blenn, M Malanga

  • 1Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Winterthurerstrasse 260, 8057, Zurich, Switzerland.

Cellular and Molecular Life Sciences : CMLS
|January 19, 2008
PubMed

Insights

Poly(ADP-ribose) (PAR) signals DNA damage-induced cell death by translocating apoptosis-inducing factor (AIF). Poly(ADP-ribose) polymerase-1 (PARP-1) is crucial for this PAR-mediated AIF signaling and cell death pathway.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Poly(ADP-ribose) (PAR) acts as a cellular signal for DNA damage, initiating cell death pathways.
  • PAR facilitates the translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus, triggering cell death.
  • The dynamic nature of PAR molecules is influenced by cellular stress.

Purpose of the Study:

  • To investigate the roles of key enzymes in PAR metabolism—poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG)—in DNA damage-induced cell death.
  • To determine the specific contribution of PARP-1, PARP-2, and PARG to alkylation-induced cell death and AIF translocation.

Main Methods:

  • Utilized RNA interference (RNAi) to specifically inhibit the expression of PARP-1, PARP-2, and PARG.
  • Induced cell death using an alkylating agent to mimic DNA damage.
  • Monitored AIF translocation from mitochondria to the nucleus.

Main Results:

  • Poly(ADP-ribose) polymerase-1 (PARP-1) significantly contributed to cell death induced by the alkylating agent.
  • PARP-1, but not PARP-2 or PARG, was essential for the translocation of apoptosis-inducing factor (AIF).
  • The study identified PARP-1 as a critical enzyme in generating the PAR signal that mediates AIF translocation and subsequent cell death.

Conclusions:

  • PARP-1 plays a pivotal role in DNA damage-induced cell death by regulating PAR synthesis and AIF translocation.
  • The findings highlight PARP-1 as a key mediator of cell death signaling, involving AIF, irrespective of the specific death pathway.
  • Targeting PARP-1 may offer therapeutic strategies for modulating cell death in response to DNA damage.

More Related Videos

Studying Ribonucleotide Incorporation: Strand-specific Detection of Ribonucleotides in the Yeast Genome and Measuring Ribonucleotide-induced Mutagenesis09:04

Studying Ribonucleotide Incorporation: Strand-specific Detection of Ribonucleotides in the Yeast Genome and Measuring Ribonucleotide-induced Mutagenesis

Published on: July 26, 2018

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...
Biosynthesis of Nucleic Acids01:28

Biosynthesis of Nucleic Acids

Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Base Excision Repair01:54

Base Excision Repair

One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
Carboxylic Acids to Methylesters: Alkylation using Diazomethane01:33

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

Carboxylic acids react with diazomethane in an ether solvent via alkylation at the carboxylate oxygen atom to give methyl esters of the corresponding acid with excellent yields.