Dave Thirumalai

Condensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular biological phenomenon. This process is driven by the formation of chromosome loops. The ATP consuming motor, condensin, interacts with chromatin segments to actively extrude loops. I will present an analytically solvable model for loop extrusion (LE) [1], which was motivated by real-time imaging experiments.  The theory suggests that condensin must undergo a large conformational change, induced by ATP binding, bringing distant parts of the motor to proximity.  Simulations using a simple model confirm that the motor transitions between an open and a closed state in order to extrude loops by a scrunching mechanism, similar to that proposed in DNA bubble formation during bacterial transcription. Changes in the orientation of the motor domains are transmitted over ~50 nm, connecting the motor head and the hinge, thus providing an allosteric basis for LE.  Extension of the theory to multiple motors [2], which was used to obtain mitotic structures will be presented.