Related Experiment Video

Updated: Jun 9, 2025

A New Toolkit for Evaluating Gene Functions using Conditional Cas9 Stabilization
08:20

A New Toolkit for Evaluating Gene Functions using Conditional Cas9 Stabilization

Published on: September 2, 2021

4.1K

The cGAS-STING pathway is an in vivo modifier of genomic instability syndromes

Marva Bergman, Uri Goshtchevsky, Tehila Atlan

    Biorxiv : the Preprint Server for Biology
    |October 28, 2024
    PubMed

    Insights

    DNA damage repair (DDR) gene mutations cause premature aging. Targeting the cGAS-STING pathway reduces inflammation and rescues aging phenotypes in a fish model, offering a potential therapeutic strategy for genomic instability.

    Area of Science:

    • Genetics
    • Molecular Biology
    • Aging Research

    Background:

    • Mutations in DNA damage repair (DDR) genes are linked to premature aging syndromes.
    • Inflammation's role in DDR pathophysiology is not fully understood.
    • Cytoplasmic DNA fragments may trigger inflammatory responses.

    Purpose of the Study:

    • To model Ataxia Telangiectasia (A-T) and Bloom Syndrome in the African turquoise killifish (N. furzeri).
    • To investigate the link between DDR defects, inflammation, and disease phenotypes.
    • To explore the therapeutic potential of targeting the cGAS-STING pathway.

    Main Methods:

    • Modeling A-T and Bloom Syndrome in N. furzeri.
    • Analyzing phenotypes including infertility, cytoplasmic DNA, and lifespan.
    • Investigating the cGAS-STING pathway and interferon signaling.
    • Generating cGAS mutants to assess rescue effects.

    Main Results:

    • Replication of key DDR syndrome phenotypes in killifish.
    • Identification of cytoplasmic DNA activating the cGAS-STING pathway and interferon signaling.
    • Partial rescue of germline defects and senescence in A-T fish by mutating cGAS.
    • Reversal of telomere abnormalities and suppression of transposable elements in double mutants.

    Conclusions:

    • Interferon signaling plays a significant role in A-T pathology.
    • The cGAS-STING pathway acts as a non-canonical inhibitor of DDR.
    • The cGAS-STING pathway is a potential therapeutic target for genomic instability syndromes.

    More Related Videos

    Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter06:59

    Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter

    Published on: March 31, 2022

    2.4K
    Optogenetic Random Mutagenesis Using Histone-miniSOG in C. elegans04:51

    Optogenetic Random Mutagenesis Using Histone-miniSOG in C. elegans

    Published on: November 14, 2016

    9.0K

    Related Concept Videos

    Mutagenicity and Carcinogenicity01:25

    Mutagenicity and Carcinogenicity

    Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
    1.2K
    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
    Epigenetic Regulation01:37

    Epigenetic Regulation

    Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
    X-chromosome...
    3.0K
    Induced Pluripotent Stem Cells01:06

    Induced Pluripotent Stem Cells

    Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
    Somatic...
    3.9K
    Genomic Imprinting and Inheritance02:30

    Genomic Imprinting and Inheritance

    Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
    The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
    33.4K