SFB1551 Project: R10

Project Title: A coarse-grained model for investigating DNA loop extrusion

Summary: Structural Maintenance of Chromosomes (SMC) complexes are essential molecular machines that play a central role in the organization, regulation, and maintenance of the genome. A phenomena common to all SMC complexes is loop extrusion, a process that dynamically reorganizes chromatin by forming and enlarging DNA loops. Loop extrusion is implicated in diverse cellular processes, including DNA compaction, replication, and transcriptional regulation. Despite its importance, the detailed molecular mechanisms governing how SMC complexes regulate loop extrusion in the crowded and heterogeneous nuclear environment remain incompletely understood.

To address these questions, we combine state-of-the-art single-molecule experiments with predictive coarse-grained molecular simulations. In our model, DNA is represented as a semi-flexible bead–spring polymer, allowing us to probe loop-extrusion dynamics at experimentally relevant length and time scales. This integrative approach enables us to both interpret and validate experimental observations, and to uncover new mechanistic insights into the operation of SMC complexes.