Abstract
SummaryThe spatial organization of chromosomes by structural maintenance of chromosomes (SMC) complexes is vital to organisms from bacteria to humans1,2. SMC complexes were recently found to be motors that extrude DNA loops3–11. It remains unclear, however, what happens when multiple SMC complexes encounter one anotherin vivoon the same DNA, how encounters are resolved, or how interactions help organize an active genome12. Here, we set up a “crash-course track” system to study what happens when SMC complexes encounter one another. Using theparS/ParB system, which loads SMC complexes in a targeted manner13–17, we engineered theBacillus subtilischromosome to have multiple SMC loading sites. Chromosome conformation capture (Hi-C) analyses of over 20 engineered strains show an amazing variety of never-before-seen chromosome folding patterns. Polymer simulations indicate these patterns require SMC complexes to traverse past each otherin vivo, contrary to the common assumption that SMC complexes mutually block each other’s extrusion activity18. Our quantitative model of bypassing predicted that increasing the numbers of SMCs on the chromosome could overwhelm the bypassing mechanism, create SMC traffic jams, and lead to major chromosome reorganization. We validated these predictions experimentally. We posit that SMC complexes traversing one another is part of a larger phenomenon of bypassing large steric barriers which enables these loop extruders to spatially organize a functional and busy genome.
Publisher
Cold Spring Harbor Laboratory
Cited by
6 articles.
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