2023-10-01 06:00:04
Gene expression, through the formation of toxic hybrids between mRNA and DNA, can lead to mutations or other forms of genetic alterations. In an article published in the journal Nature Communications, scientists combined approaches from imaging and biochemistry. scientist who studies the chemical reactions taking place…) to show that the genes forming (In intonation, changes in fundamental frequency are perceived as variations of…) these structures were supported (The payload ( payload in English; the payload) represents what is actually…) and conducted towards the nuclear pores in order to protect the integrity of the genome (The genome is all of the genetic material of an individual or an. ..).
Image d’illustration Pixabay
Maintaining genome stability requires highly regulated coordination of different activities that target DNA. High transcription rates can notably lead to the appearance of DNA/mRNA hybrids or “R-loops”, toxic structures which disrupt replication and lead to the appearance of damage in the DNA. How do cellular machineries regulate gene activity without jeopardizing the integrity of genetic material? This is the question that scientists tried to answer in this study.
Using genome-wide approaches and live cell microscopy, scientists studied the localization of genes forming “R-loop” structures, inside the yeast nucleus (A yeast is a unicellular fungus capable of cause fermentation of materials…) S. cerevisiae. They were thus able to show that the single strand of DNA present within these structures was first detected by the trimeric RPA (replication protein A) protein, an essential factor previously implicated in DNA replication and repair.
They were also able to establish that the coupling of this protein to the small polypeptide SUMO (small ubiquitin-like modifier) then allowed “labeling” of the genes concerned, ensuring their interaction (An interaction is an exchange of information, affects or of energy between two agents within…) with components of the nuclear pore (The term nuclear energy covers two meanings depending on the context:), known for its role in the exchange of molecules between the nucleus and the rest of the cell. In this environment (The environment is everything that surrounds us. It is all the natural elements and…), the elimination of “R-loops”, a process possibly facilitated by the export of the mRNAs involved , via the pores, would thereby prevent the associated genetic instability.
A balance between high gene expression and maintaining DNA stability
For scientists, similar mechanisms had already been observed in various situations where the cell’s DNA is subjected to damage or treatments that alter its genetic integrity. In this context, the reorganization of damaged DNA allows its repair at the level of nuclear pores. When genes are very actively expressed, particularly in response to stress (stress (“constraint” in English), or general syndrome, etc.), these mechanisms would therefore make it possible to reconcile high gene expression (ie high rates of synthesis of mRNA) and the preservation of DNA stability, minimizing the risks of mutations or genetic damage caused by “R-loops”.
These results thus shed new light on the detection mechanisms of these structures, paving the way for understanding their roles in the biology of genomes, but also in the various human pathologies with which they have been associated, in particular cancers or syndromes. neurological.
A, A model for the detection and relocation of “R-loops” in the nucleus.
B, Detection by microscopy on living yeast of a gene forming “R-loops” (in orange), positioned at the level of nuclear pores (in blue).
© B. Palancade – IJM/CNRS
Reference
A R-loop sensing pathway mediates the relocation of transcribed genes to nuclear pore complexes.
Penzo A, Dubarry M, Brocas C, Zheng M, Mangione RM, Rougemaille M, Goncalves C, Lautier O, Libri D, Simon MN, Geli V, Dubrana K, Palancade B.
Nature communications. 14(1):5606. Published online: 20 Sept 2023.
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