Supercoiling of the DNA helix - a positive force in chromosome organization and function.

Cellular function and organism development require a multitude of factors that transcribe, duplicate, repair, and segregate chromosomal DNA.

These processes depend on the three-dimensional (3D) organization of chromosomes and are influenced by changes in the helical structure of DNA, so called supercoiling.

Contrary to the expectations in the field, we have revealed that DNA supercoiling controls chromosome 3D organization via a family of chromosome-folding machines called SMC protein complexes (e.g., Nature 2011; Cell Reports 2015, Science Adv. 2022, Nature 2023; Mol. Cell 2024). This opens a new fundamental area of chromosome research which we will explore during the coming eight years.

The specific aims are to determine:The molecular details of the DNA supercoiling / SMC complex / chromosome organization interplay.The impact of this interplay on a) early development and b) inhibition of virus duplication.

The project builds upon an international research environment that unite a wide variety of expertise, and methods such as single molecule analysis, high resolution microscopy, bioinformatics, in vivo models, and a unique marker for chromosomal supercoiling we recently discovered.

Given the fundamental nature of DNA supercoiling, and the vital roles of SMC complexes and chromosome 3D organisation, these investigations will close a significant gap in our understanding of chromosome dynamics and function.