Your DNA is constantly damaged by sources both inside and out of your body. One particularly serious damage, called a double circuit break, involves termination of both DNA double spiral strands.
Double -circuit breaks are one of the most severe forms of DNA lesions to repair cells because they disrupt DNA continuity and leave an intact template to substantiate new strands. If this is wrong, these breaks can lead to other mutations that make the genome unstable and increase the risk of many diseases, including cancer, neurodegeneration and immunodeficiency.
The cells first restore the fractures of the double circuit, re -joining the broken ends of the DNA or using another DNA molecule as a repair template. However, my team and I have learned that RNA, the type of genetic material, best known for its role in the production of proteins, is surprisingly playing a key role in facilitating these harmful breaks.
These insights could not only prepare the way for new genetic disorders, cancer and neurodegenerative disease treatment strategies, but also strengthen gene editing technologies.
Seal the knowledge gap in DNA correction
I have spent the last two decades exploring the RNA and DNA connection to understand how cells maintain the integrity of the genome and how these mechanisms could be used for genetic engineering.
The long -term issue in this area was whether RNA cells help to maintain the genome stable not only as a copy of DNA in the production of proteins and gene expression regulators. To explore how RNA could do this, it was particularly difficult because of the similarity to DNA and how quickly it worsens. It is also technically difficult to say whether RNA is directly seeking to repair DNA or indirectly regulates the process. Traditional models and tools for the study of DNA were mainly concentrated on protein and DNA, leaving a possible RNA contribution to substantially unusual.
For my team and I was wondering whether RNA could be actively involved in repairing double -circuit breaks as the first line of defense. To investigate this, we used the gene editing tool CRISPR-CAS9 to take breaks in specific places in human and yeast cell DNA. We then analyzed how RNA influences various aspects of the repair process, including efficiency and results.
We have found that RNA can be actively leading the double -circuit break repair process. This is done by connecting to the broken ends of the DNA, helping to match the DNA sequences on a matched circuit that is not broken. It can also seal the gaps either removed segments, even more affected, or how the original sequence is restored.
In addition, we found that RNA helps to restore double -circuit breaks in both yeast and human cells, which indicates that its role for DNA restoration is evolutionary preserved among species. It is noteworthy that even the low level of RNA was sufficient to influence the efficiency and results of the reconstruction, as demonstrates its extensive and previously unrecognized function in maintaining the stability of the genome.
RNA controlled
Our conclusions show how RNA can directly contribute to the stability and development of the genome by disclosing an unknown RNA function to restore DNA violations. This is not only a passive messenger, but also an active participant of genome care.
These insights could help researchers create new ways to direct genome instability based on many diseases, including cancer and neurodegeneration. Traditionally, treatments and gene editing measures were concentrated almost only on DNA or protein. Our conclusions show that RNA modification in different ways could also affect how cells respond to DNA damage. For example, researchers could design RNA -based treatments to increase harmful breaks that can cause cancer, repair or selectively disrupt DNA breaks in cancer cells to help kill them.
In addition, these data could improve the accuracy of gene editing technologies such as CRISPR, taking into account RNA and DNA interaction at the cut site. This could reduce the targeted effect and increase edit accuracy, and eventually contribute to the safer and more efficient gene therapy.
There are still many unanswered questions about how the RNA interacts with the DNA repair process. The evolutionary role played by the RNA in maintaining the stability of the genome is also unclear. But one thing is real: RNA is no longer just a messenger, a molecule that has a direct hand in DNA repair, rewriting what researchers know about how cells protect their genetic code.
This article has been published from a conversation, non -profit, independent news organizations that provide you with facts and reliable analysis to help you give meaning to our complex world. It was written by: Francesca Storici, Institute of Georgia Technology
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Francesca Storici advises Tessera Therapeutics. She received funding from the National Institutes of Health and the National Science Foundation.