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In the field of molecular biology, Understand how DNA organizes within our cells is essential to decipher the functioning of genes. For decades scientists have studied how certain proteins shape and structure genetic material, a key process for the activation and regulation of genes. A new study, led by researchers from the Netherlands, Austria and Switzerland, has revealed an unexpected mechanism in this process, solving a long -standing scientific controversy.
The finding focuses on proteins known as SMC complexes (Structural Maintenance of Chromosomes)that remodel the DNA forming ties. Until now, it was thought that these molecular engines operated in one direction or symmetrically from both ends. However, new experiments have shown that they can change direction dynamicallywhat could rewrite our understanding of genome architecture and open new ways for the study of genetic diseases.
The key role of SMC complexes in DNA organization
SMC complexes are essential for DNA organization in all eukaryotic cells. These molecular engines have the capacity to Reconfigure DNA forming loopsa critical process for the regulation of gene expression and the maintenance of genome stability. There are several types of SMC complexes, among them Cohesin, Condensina and SMC5/6each with specific functions.
Until now, the studies suggested that some SMC complexes were symmetrical, incorporating DNA on both sides to form a loop, while others were asymmetric, attracting DNA only from one side. This apparent contradiction has generated debates in the scientific community, without a clear response on how these molecular engines really work.
The new study Solve this paradox by demonstrating that All SMC complexes work asymmetricallybut with the ability to Invest your addresswhich gave the illusion of a symmetrical movement in certain cases.
A possible finding thanks to avant -garde technology
To demonstrate this hypothesis, the researchers used single molecule microscopyan advanced technique that allows visualizing individual proteins in action on DNA. This approach has been crucial to unravel the true behavior of SMC complexessince in previous experiments with less precise techniques, the changes of direction went unnoticed.
The observations revealed that, instead of moving unidirectionally, SMC engines capture DNA on one side, then change direction and incorporate it from the other, generating a highly dynamic loop pattern. This behavior was observed in cohesine, condensin and SMC5/6, indicating that It is a universal mechanism in eukaryotic organisms.
The molecular switch: the Nipbl protein
The study also identified a key element in this process: the Nipbl proteinwhich acts as a “steering switch” on SMC engines. When NIPBL joins the SMC complex, this maintains an DNA extrusion address. However, when Nipbl dissociates and then reincorporates, the engine changes direction.
This discovery has important implications for cell biology, since it suggests that cells can Actively modulate DNA folding addresswhat could be fundamental for processes such as gene regulation, DNA repair and chromosomal segregation during cell division.
Implications for the study of genetic diseases
One of the most promising aspects of this finding is its Relevance for medicine and research in genetic diseases. Mutations in genes coding for SMC and NIPBL proteins have been associated with disorders such as Lango’s Cornelia syndromea rare disease that affects fetal development.
On the other hand, the defective regulation of SMC engines has also been involved in certain types of cancer and neurodegenerative diseases. Understand how these complexes mold DNA and how their alterations can lead to the disease could open new therapeutic strategies to correct failures in the organization of the genome.
An impact advance in multiple areas
The discovery that SMC complexes can change direction while remodeling DNA Solve a long data debate and provide a new perspective on the dynamics of genome organization.
From a fundamental point of view, this expands our understanding of molecular biology and mechanics of chromosomes. At the applied level, the finding could contribute to the development of new medical strategies to treat diseases caused by failures in DNA architecture. With increasingly precise tools to study molecular dynamics, in the coming years they promise More revolutionary advances in the understanding and manipulation of the human genome.
References
- Barth, R., Davidson, If, Van der Torre, J., Taschner, M., Gruber, S., Peters, Jm., & Dekker, C. (2025). SMC Motor Proteins Extrude DNA Asymmetricly and contain a direction switch. Cell. Doi: 10.1016/J.cell.2024.12.020.
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