![]() ![]() Once a cell duplicates a chromosome, the two identical chromosomes must be held together until the cell is ready to divide in two. It does this by duplicating its chromosomes (the DNA molecules that encode the genome) and distributing one copy of each to its daughter cells. When a cell divides, it has to ensure that each of its daughter cells inherits one copy of its genetic information. Loop extrusion by biased Brownian motion has important implications for chromosomal cohesin function. ![]() Our model extends to asymmetric and symmetric loop extrusion, as well as z-loop formation. Molecular-mechanical simulations of gripping state formation and resolution cycles recapitulate experimentally observed DNA loop extrusion characteristics. If head gate passage fails, hinge module motion creates a Brownian ratchet that, instead, drives loop extrusion. Gripping state disassembly, following ATP hydrolysis, triggers unidirectional hinge module movement, which completes topological DNA entry by directing DNA through the ATPase head gate. Two HEAT-repeat DNA binding modules, associated with cohesin’s heads and hinge, are now juxtaposed. ATP and DNA binding promote cohesin conformational changes that guide DNA through a kleisin N-gate into a DNA gripping state. Here, we propose a structure-based model explaining both activities. Alternatively, cohesin extrudes DNA loops, thought to reflect chromatin domain formation. The cohesin complex topologically encircles DNA to promote sister chromatid cohesion. ![]()
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