Biophysical principles of chromosome organization
In each human cell, 2 meter DNA is physically compacted into chromosomes that are packed into a micrometer-sized nucleus, but the mechanism by which the extremely long and negatively charged polymer is compacted into this tiny structure remains elusive. Structural Maintenance of Chromosome (SMC) protein complexes such as cohesin and condensin are the key organizers of the spatiotemporal structure of chromosomes by extruding DNA loops1. In our work using liquid-phase High-Speed Atomic Force Microscopy (HS AFM) and magnetic tweezers (MT)1,2, we were the first to obtain experimental data for yeast condensin acting on individual DNA molecules. The findings suggest a scrunching model in which the SMC complex extrudes a DNA loop by a cyclic switching of its conformation between open and collapsed shapes. In addition, we show that yeast cohesin complexes unexpectedly can exhibit a new type of phase separation, called a Bridging-Induced Phase Separation (BIPS) that is induced by bridging of distant regions on a long DNA by proteins that possess multiple DNA-binding sites3. Our findings suggest that both DNA loop extrusion and phase separation by SMC complexes are fundamental building blocks of chromosome organization. Lastly, for future works, I propose various biophysical studies to shed light on the universal and fundamental principles of phase separation that constitute membraneless organelles in chromosome.
- Ryu, J.-K. et al. The condensin holocomplex cycles dynamically between open and collapsed states. Nat. Struct. Mol. Biol. 27, 1134–1141 (2020).
- Ryu, J. K., Rah, S. H., Janissen, R., Kerssemakers, J. W. J. & Dekker, C. Resolving the step size in condensin ‐ driven DNA loop extrusion identifies ATP binding as the step ‐ generating process. Nucl. Acids Res., Under review (2021), Bioarxiv doi:10.1101/2020.11.04.368506.
- Ryu, J.-K. et al. Bridging-induced phase separation induced by cohesin SMC protein complexes. Sci. Adv. 7, eabe5905 (2021).