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smc protein DNS looping discovery

Revolutionary Discovery: Molecular Machines Twist DNA While Looping Chromosomes

Groundbreaking Discovery by Researchers from TU Delft and IMP Vienna Biocenter

Illustration of SMC proteins twisting and looping DNA, revealing new molecular mechanisms critical for chromosome function.

Researchers from the Kavli Institute at Delft University of Technology and the IMP Vienna Biocenter have uncovered a novel characteristic of the molecular motors responsible for shaping chromosomes. Building on their discovery six years ago that SMC motor proteins create extended loops in DNA, they have now revealed that these motors also introduce substantial twists within the loops they form.

Understanding the Impact of DNA Twisting on Chromosome Structure and Function

This research enhances our understanding of chromosome structure and function, shedding light on how disruptions in twisted DNA looping may contribute to health conditions such as developmental disorders like cohesinopathies. The findings were published in Science Advances.

The Challenge of Packing DNA into the Nucleus

Consider the challenge of fitting two meters of rope into a space smaller than the tip of a needle-this is akin to the task every cell faces when organizing its DNA within the tiny nucleus. To manage this, nature uses remarkable methods, such as coiling the DNA into supercoils and wrapping it around specialized proteins for efficient storage.

Tiny DNA Loop Play a Critical Role in Regulating Chromosome Functions

The Role of SMC Proteins in DNA Looping and Chromosome Structure

Compaction alone is insufficient; cells must also regulate chromosome structure to facilitate its function. For instance, when genetic information is required, the DNA is read locally. Specifically, during cell division, the DNA must first unwind, replicate, and then ensure proper separation into two daughter cells.

The Discovery of SMC Complexes and Their Role in DNA Looping

SMC complexes (structural maintenance of chromosomes), specialized protein machines, are essential for these processes. Only a few years ago, researchers at Delft and elsewhere discovered that SMC proteins act as molecular motors, forming long loops in DNA, which are crucial for regulating chromosome function.

Pioneering Research Using Magnetic Tweezers to Observe SMC Protein Behavior

Observing DNA Looping and Twisting in Real Time

At Cees Dekkar's lab at TU Delft, postdocs Richard Janissen and Roman Bath have uncovered important insights to solve this puzzle. They pioneered a new method using "Magnetic Tweezers," enabling them to observe individual SMC proteins making looping movements in DNA.

A Key Breakthrough: SMC Proteins Twist DNA During Looping

An important breakthrough was their ability to observe whether the SMC protein modifies the twist in the DNA. Interestingly, the team found that it does: the human SMC protein cohesin not only loops the DNA but also twists it in a left-handed direction, adding 0.6 turns with each loop formed.

Understanding the Evolutionary Path of SMC Proteins

Evolutionary Consistency in DNA Looping and Twisting Mechanisms

In addition, the team found that this twisting action is not confined to humans. SMC proteins in yeast show identical behavior. Interestingly, all SMC proteins from both humans and yeast twist DNA by 0.6 turns with each extrusion step. This finding indicates that the DNA extrusion and twisting processes have remained consistent throughout evolution.

A Universal Mechanism for DNA Looping Across Species

Whether the DNA is looped in humans, yeast, or any other cell, nature follows the same approach.

Implications of DNA Looping for Gene Expression and Health

The Role of DNA Looping in Supercoiling and Gene Expression

These new discoveries offer crucial insights into deciphering the molecular mechanism behind this novel motor type. Furthermore, they reveal that DNA looping influences the supercoiling state of chromosomes, which in turn impacts key  processes such as gene expression.

SMC Proteins and Their Link to Genetic Disorders

Understanding the Link Between SMC Proteins and Cornelia de Lange Syndrome

Finally, the SMC proteins are linked to a number of disorders, such as Cornelia de Lange Syndrome. Gaining insights into these processes is vital for pinpointing the molecular causes of these serious diseases.

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