Related Experiment Video

Updated: Jun 22, 2025

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

33.3K

MRE11 and TREX1 control senescence by coordinating replication stress and interferon signaling

Hervé Técher1,2, Diyavarshini Gopaul1,3, Jonathan Heuzé1

  • 1Institut de Génétique Humaine, University of Montpellier, CNRS, Equipe Labellisée Ligue contre le Cancer, Montpellier, France.

Nature Communications
|June 26, 2024
PubMed

Insights

Oncogene-induced senescence (OIS) relies on DNA damage response (DDR) and the cGAS-STING pathway. This study reveals that the MRE11 nuclease and type I interferons (IFNs) create a feedback loop amplifying DDR during OIS.

Area of Science:

  • Cellular senescence
  • DNA damage response
  • Innate immunity

Background:

  • Oncogene-induced senescence (OIS) is a tumor suppressive mechanism involving cell cycle arrest.
  • OIS activation requires the DNA damage response (DDR) and the cGAS-STING pathway, which produces type I interferons (IFNs).
  • The interplay between replication stress (RS) and IFN responses in OIS is not fully understood.

Purpose of the Study:

  • To investigate the cooperative mechanisms between replication stress and IFN responses in OIS.
  • To elucidate the roles of MRE11 nuclease and TREX1 in regulating OIS.

Main Methods:

  • Utilized H-RASV12 oncogene in immortalized human fibroblasts.
  • Employed MRE11 inhibitor Mirin and manipulated TREX1 expression.
  • Assessed replication stress, micronuclei formation, and IFN response.

Main Results:

  • MRE11 activity is essential for RASV12-induced OIS, RS, and IFN response.
  • Inhibition of MRE11 or TREX1 overexpression abrogated OIS.
  • TREX1 inhibition or IFN-β treatment induced RS and DNA damage independently of RASV12.

Conclusions:

  • The IFN response acts as a positive feedback loop to enhance DDR during OIS.
  • MRE11 and TREX1 are key regulators of this feedback mechanism.
  • Findings reveal a novel crosstalk between DDR and innate immunity in OIS.

More Related Videos

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

8.1K
Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

13.9K

Related Concept Videos

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
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
23.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Replication in Eukaryotes01:29

Replication in Eukaryotes

In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
13.7K
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...
9.1K