Looping the genome with SMC complexes: insights from single-molecule analysis

In all organisms, chromosomes must be compacted by nearly three orders of magnitude to fit within the confines of the cell, while still permitting a wide range of essential genomic processes. Yet, the fundamental principles underlying the formation and regulation of 3D genome architecture remain poorly understood. My lab aims to understand the molecular mechanisms governing 3D genome organization and what functional consequences arise from the spatial regulation of genomes. Our specific focus is on Structural Maintenance of Chromosomes (SMC) ATPase motor complexes, which drive genome folding through DNA loop extrusion. We take a multidisciplinary approach—combining single-molecule imaging, structural biology, and biochemistry—to visualize loop extrusion in real time and dissect its molecular basis.
In this talk, I will present recent findings from my lab across a variety of SMC complexes, including Smc5/6, bacterial Wadjet, and condensin II. These include the discovery of loop extrusion activity in Smc5/6 [1] and its role in organizing transcriptionally active, positively supercoiled genomic regions [2]; the identification of bacterial Wadjet SMC complexes as contributors to DNA-based immunity through loop-extrusion–mediated plasmid recognition [3]; and our most recent insights into the mechanisms of condensin II self-inhibition and activation [4]. I will conclude with an outlook on our future research directions.
[1] Pradhan et al. Nature 616, 843–848 (2023)
[2] Jeppsson et al. Mol. Cell 84(5) (2024)
[3] Pradhan et al. Mol. Cell 85(1) (2025)
[4] Unpublished