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    Home > Active Ingredient News > Study of Nervous System > Science: Using limited DNA repair on the "knife edge", neurons will give priority to preventing aging and disease!

    Science: Using limited DNA repair on the "knife edge", neurons will give priority to preventing aging and disease!

    • Last Update: 2021-04-19
    • Source: Internet
    • Author: User
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    DNA damage repair is a key mechanism for cells to maintain normal function.

    However, for the longest-lived neurons (nerve cells) in the human body, due to the lack of DNA replication capabilities, they can only rely on a limited DNA repair mechanism to maintain the integrity of the genome.

    The already limited repair mechanism will decline with age, which explains why people suffer from age-related neurodegenerative diseases when aging, such as Alzheimer's disease and Parkinson's disease.

    But in this process, how the instability of the genome is generated, and what strategies neurons and other long-lived cells will evolve to protect their genome stability, scientists still know little about this.

    In a new study published in Science on April 2, Beijing time, a research team led by the Salk Institute of Biology in the United States found that neurons will use limited repair mechanisms on the "blade", focusing on repairing and "Hot spots" related to aging and disease, and these genomic sites are always at the forefront of repair work because they play a key role in neurological function.

    The results of the study provide important insights into the genetic structure of aging and neurodegenerative diseases, and open up new avenues for the development of treatments for Alzheimer’s, Parkinson’s and other age-related diseases.

    The corresponding author of the study, Professor Rusty Gage, director of the Salk Institute of Biology, said: "This study shows for the first time that when it comes to repair, neurons will prioritize certain key parts of the genome.

    These findings have changed our perception of many age-related issues.
    View of neurological diseases and the possibility of exploring DNA repair as a new treatment method.

    "In order to understand how neurons maintain the stability of their genomes during aging, researchers have developed a method that is induced in human embryonic stem cells.
    The method of locating DNA repair in the neuron genome is called "Repair-seq".They made neurons from stem cells and added synthetic nucleoside analogs.

    These artificial nucleosides can be discovered through DNA sequencing and imaging to show where neurons use them to repair DNA damaged by normal cellular processes.

    Researchers are surprised that neurons are so focused on protecting key parts of the genome.

    Dylan Reid, co-corresponding author of the study and a postdoctoral researcher in the Genetics Laboratory, said: “This is really incredible! What we see is a very clear repair area.

    The proteins on these'hot spots' are related to neurodegenerative diseases, but also It is related to aging.

    "Researchers have found about 65,000 "hot spots" in total, covering about 2% of neuronal genomes.

    Then, they used proteomics methods to detect the proteins found in the hot spots, and determined that these hot spots are rich in histone H2A subtypes and RNA-binding proteins, etc.
    , which are all related to the evolutionary conservation of the human genome, as well as to aging and neurological diseases.
    .

    These findings provide a basis for understanding the integrity of the genome.

    In addition, when cells are treated with DNA damaging agents, many of these hotspots are also quite stable, and the most stable hotspots are closely related to the sites where chemical markers (methylation) attach, and these hotspots are also the most predictive of neuron age.
    .

    Past research has focused on identifying damaged parts of DNA, but for the first time this research has turned to finding which regions of the genome are being repaired.

    Reid said: "We changed the pattern of looking for damage to looking for repair points, which is why we found these hot spots.

    This is a new biological mechanism that may eventually change our understanding of the nervous system.

    Our understanding of this.
    The more you learn, the better you can find therapies for age-related diseases.

    "Researchers said that understanding which regions of the genome are vulnerable to damage is a very meaningful topic for them.

    Repair-seq will be a powerful research tool that can be used on this subject.

    They said that they will continue to explore more new methods to study the integrity of the genome, especially in the areas of aging and disease.

    The link to the paper: https://science.
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