Related Experiment Video

Updated: Dec 7, 2025

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.6K

Ewing sarcoma protein promotes dissociation of poly(ADP-ribose) polymerase 1 from chromatin

Seon-Gyeong Lee1,2, Namwoo Kim1,2, Su-Min Kim1,2

  • 1Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.

EMBO Reports
|October 2, 2020
PubMed

Insights

The Ewing's sarcoma breakpoint region 1 (EWS) protein regulates Poly(ADP-ribose) polymerase 1 (PARP1) dissociation from DNA. EWS inactivation causes PARP1 accumulation, excessive PARylation, and cell death, highlighting EWS's role in DNA repair.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • Poly(ADP-ribose) polymerase 1 (PARP1) is crucial for DNA damage response (DDR).
  • The Ewing's sarcoma breakpoint region 1 (EWS) protein's physiological role is largely unknown, though its fusion with FLI1 drives sarcoma.
  • EWS's interaction with PARP1 in DDR is not well understood.

Purpose of the Study:

  • To elucidate the physiological role of EWS in regulating PARP1 activity.
  • To investigate how EWS influences PARP1's interaction with damaged DNA.
  • To determine the consequences of EWS dysfunction on PARP1 accumulation and cellular viability.

Main Methods:

  • In vitro and in vivo cellular and animal models.
  • Analysis of PARP1 dissociation from damaged DNA.
  • Assessment of Poly(ADP-Ribosy)lation (PARylation) levels.
  • Genetic manipulation of EWS and PARP1, including double mutants.
  • Evaluation of survival rates and compensatory mechanisms.

Main Results:

  • EWS is essential for the dissociation of PARP1 from damaged DNA.
  • EWS inactivation leads to aberrant PARP1 accumulation and excessive PARylation, causing cell death.
  • The RGG domain of EWS mediates PAR chain interaction and PARP1 dissociation.
  • Ewing's sarcoma cells and patient tissues exhibit increased PARylation, linked to EWS fusion proteins.

Conclusions:

  • EWS plays a critical role in removing PARP1 from damaged chromatin, impacting DNA repair.
  • Dysregulation of the EWS-PARP1 axis contributes to cellular demise and may be relevant in Ewing's sarcoma.
  • Targeting PARP1 or related pathways could offer therapeutic strategies for EWS-associated conditions.
Keywords:
EWSPARDNA damage responsePARP-1PARylation

More Related Videos

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

3.0K
Single-Molecule Imaging of EWS-FLI1 Condensates Assembling on DNA07:05

Single-Molecule Imaging of EWS-FLI1 Condensates Assembling on DNA

Published on: September 8, 2021

2.6K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
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,...
6.1K
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
9.1K
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...
4.6K
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
6.5K
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:
7.6K