Related Experiment Video

Updated: Jul 5, 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

10.3K

PARP1, DIDO3, and DHX9 Proteins Mutually Interact in Mouse Fibroblasts, with Effects on DNA Replication Dynamics,

Agnes Fütterer1, Sara Rodriguez-Acebes2, Juan Méndez2

  • 1Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain.

Cells
|January 22, 2024
PubMed

Insights

Poly (ADP-ribose) polymerase 1 (PARP1), DIDO3, and DHX9 proteins form a complex regulating R-loops. This complex prevents DNA replication stress and senescence, crucial for preventing diseases like cancer.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • R-loops are essential for gene expression but their dysregulation causes DNA replication stress, linked to diseases and cancer.
  • PARP1, DIDO3, and DHX9 are key proteins involved in R-loop metabolism.
  • Previous work established an interaction between DIDO3 and DHX9.

Purpose of the Study:

  • To investigate the functional relationship between PARP1, DIDO3, and DHX9 in R-loop regulation.
  • To determine the impact of DIDO3 C-terminal truncation on protein interactions and cellular processes.
  • To explore the role of this protein complex in preventing DNA replication stress and oncogenic transformation.

Main Methods:

  • Co-immunoprecipitation assays to confirm protein interactions in mouse embryonic fibroblasts.
  • Analysis of DNA replication stress markers and senescence.
  • In vitro oncogenic transformation assays and immortalization studies.

Main Results:

  • PARP1, DIDO3, and DHX9 form a ternary complex dependent on PARP1 activity.
  • DIDO3 C-terminal truncation disrupts this complex, leading to increased replication stress and senescence.
  • DIDO3 truncation confers partial resistance to oncogenic transformation, reversible by immortalization.

Conclusions:

  • The PARP1-DIDO3-DHX9 ternary complex is critical for maintaining R-loop homeostasis.
  • Dysregulation of this complex contributes to DNA replication stress, senescence, and potentially cancer development.
  • Targeting this complex may offer therapeutic strategies for R-loop-associated diseases.
Keywords:
DHX9DIDO3Dido1 genePARP1oncogenic transformationreplication forkreplication stresssenescence

More Related Videos

Laser Micro-Irradiation to Study DNA Recruitment During S Phase07:11

Laser Micro-Irradiation to Study DNA Recruitment During S Phase

Published on: April 16, 2021

4.3K
Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay10:32

Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay

Published on: February 3, 2022

6.2K

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:37

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...
9.2K
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,...
5.8K
The DNA Replication Fork01:02

The DNA Replication Fork

An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
36.0K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K
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...
4.5K
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K