PT  - JOURNAL ARTICLE
AU  - Edward J. Banigan
AU  - Aafke A. van den Berg
AU  - Hugo B. Brandão
AU  - John F. Marko
AU  - Leonid A. Mirny
TI  - Chromosome organization by one-sided and two-sided loop extrusion
AID  - 10.1101/815340
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 815340
4099  - http://biorxiv.org/content/early/2020/04/02/815340.short
4100  - http://biorxiv.org/content/early/2020/04/02/815340.full
AB  - SMC complexes, such as condensin or cohesin, organize chromatin throughout the cell cycle by a process known as loop extrusion. SMC complexes reel in DNA, extruding and progressively growing DNA loops. Modeling assuming two-sided loop extrusion reproduces key features of chromatin organization across different organisms. In vitro single-molecule experiments confirmed that yeast condensins extrude loops, however, they remain anchored to their loading sites and extrude loops in a “one-sided” manner. We therefore simulate one-sided loop extrusion to investigate whether “one-sided” complexes can compact mitotic chromosomes, organize interphase domains, and juxtapose bacterial chromosomal arms, as can be done by “two-sided” loop extruders. While one-sided loop extrusion cannot reproduce these phenomena, variants can recapitulate in vivo observations. We predict that SMC complexes in vivo constitute effectively two-sided motors or exhibit biased loading and propose relevant experiments. Our work suggests that loop extrusion is a viable general mechanism of chromatin organization.Impact statement We reconcile seemingly contradictory findings of single-molecule and in vivo experiments on a major mechanism of chromosome organization by computationally investigating mechanisms of loop extrusion that are consistent with both.