Scientists have identified an intriguing new characteristic of the molecular motors responsible for shaping our chromosomes. Six years ago, they discovered that the SMC motor proteins create long loops in our DNA. Their recent findings reveal that these motors also introduce notable twists into these loops. This discovery enhances our comprehension of chromosome structure and function. Additionally, it sheds light on how disruptions in these twisted DNA loops can impact health, particularly in developmental disorders such as ‘cohesinopathies’.
Researchers from the Kavli Institute at Delft University of Technology and the IMP Vienna Biocenter have revealed a new attribute of the molecular motors that organize our chromosomes. While they uncovered six years ago that SMC motor proteins form extended loops in our DNA, they have now found these motors additionally induce significant twists in the loops they generate. These revelations deepen our understanding of both the structure and functionality of chromosomes. Moreover, they highlight the potential health effects of disturbances in these twisted DNA loops, particularly related to developmental disorders known as ‘cohesinopathies’. The findings were published in Science Advances.
The challenge our cells face
Consider the difficulty of fitting two meters of rope into an area smaller than the tip of a needle—that’s what each cell in your body encounters when packing DNA into its tiny nucleus. To manage this, nature has devised clever methods, including twisting DNA into coils within coils, referred to as ‘supercoils’ (see images for a visual representation), and wrapping it around specific proteins for better storage.
How small DNA loops manage chromosome functions
However, mere compression isn’t sufficient. Cells must also manage chromosome structure to ensure its functionality. For example, when genetic information needs to be accessed, the DNA is read in specific areas. Particularly during cell division, the DNA must first unpack, replicate, and then accurately separate into two new cells. Specialized protein machines known as SMC complexes (Structural Maintenance of Chromosomes) are vital in these operations. Just a few years back, researchers in Delft and elsewhere discovered that these SMC proteins serve as molecular motors creating extensive loops in DNA, which are essential regulators of chromosome activity.
A new revelation
In the laboratory led by Cees Dekker at TU Delft, postdoctoral researchers Richard Janissen and Roman Bath have made significant progress in unraveling this mystery. They developed an innovative technique using ‘magnetic tweezers’ that allowed them to observe individual SMC proteins making looping motions in DNA. Crucially, they were also able to determine if the SMC protein altered the twist of the DNA. Remarkably, the team found that it did; the human SMC protein cohesin not only creates a loop from the DNA but also twists the DNA counterclockwise by 0.6 turns with each looping step.
Insights into the evolution of SMC proteins
Additionally, the researchers discovered that this twisting action is not exclusive to humans. Similar SMC proteins found in yeast displayed the same behavior. Strikingly, all types of SMC proteins from both humans and yeast introduce the same level of twist—turning the DNA by 0.6 turns at every loop extrusion step. This indicates that the mechanisms for DNA extrusion and twisting have remained consistent throughout evolutionary history. Regardless of whether DNA is looped in humans, yeast, or any other organism, nature employs the same method.
Crucial insights
These latest discoveries provide essential insights into understanding the molecular operations of this novel type of motor. They also clarify that DNA looping influences the supercoiling state of chromosomes, which directly impacts processes such as gene expression. Furthermore, these SMC proteins are associated with various diseases like Cornelia de Lange Syndrome, making it imperative to better comprehend these processes to trace the molecular origins of such serious conditions.
