How SMC Proteins Twist and Loop DNA for Chromosome Function

Scientists from the Kavli Institute at Delft University of Technology and the IMP Vienna Biocenter have made a groundbreaking discovery about the role of SMC motor proteins in shaping chromosomes. Previously, they found that these proteins form long loops in DNA, but their latest research shows that these proteins also add twists to the DNA loops, which is a significant new finding.

This discovery deepens our understanding of the chromosome structure and its role in cellular function. It also provides insights into how disruptions in DNA looping and twisting can contribute to health problems, such as cohesinopathies, a group of developmental diseases linked to errors in chromosome maintenance.

Cells face the challenge of packing DNA, which can stretch up to two meters, into a tiny nucleus. To solve this, nature uses strategies like twisting the DNA into supercoils, which are coils within coils, and wrapping the DNA around proteins to keep it compact.

However, compaction alone isn’t enough. Cells must also regulate the structure of chromosomes for proper function. When genetic information needs to be accessed or when a cell divides, the DNA must be unpacked, replicated, and accurately distributed between the new cells.

The newly discovered SMC complexes, which are specialized protein machines, are essential in these processes. A few years ago, scientists revealed that SMC proteins act as molecular motors that generate DNA loops, which are crucial for regulating chromosome functions during cell activities.

In their recent study, researchers at TU Delft used magnetic tweezers to observe SMC proteins in action. They discovered that these proteins do not only create loops in DNA, but also induce a left-handed twist in the DNA by 0.6 turns with every loop they form, showing that these molecular motors have an important twisting function.

The study also revealed that this twisting mechanism is not exclusive to humans. Similar SMC proteins in yeast also add the same amount of twist to DNA during loop formation, suggesting that this process has been preserved throughout evolution across different species. This discovery provides new insights into the molecular mechanisms of DNA looping, supercoiling, and their roles in gene expression, while also shedding light on their connection to various diseases like Cornelia de Lange Syndrome.