The interplay between asymmetric and symmetric DNA loop extrusion

Abstract

Chromosome compaction is essential for reliable transmission of genetic information. Experiments suggest that ∼1000-fold compaction is driven by condensin complexes that extrude chromatin loops, by progressively collecting chromatin fiber from one or both sides of the complex to form a growing loop. Theory indicates that symmetric two-sided loop extrusion can achieve such compaction, but recent single-molecule studies (Golfier et al., 2020) observed diverse dynamics of condensins that perform one-sided, symmetric two-sided, and asymmetric two-sided extrusion. We use simulations and theory to determine how these molecular properties lead to chromosome compaction. High compaction can be achieved if even a small fraction of condensins have two essential properties: a long residence time and the ability to perform two-sided (not necessarily symmetric) extrusion. In mixtures of condensins I and II, coupling two-sided extrusion and stable chromatin binding by condensin II promotes compaction. These results provide missing connections between single-molecule observations and chromosome-scale organization.

Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells

“…These data support a model in which multiple condensins bind L-CID boundaries and extrude loops in opposite directions, possibly through a version of the handcuff model in which an anti-parallel dimer of condensins is loaded at boundaries (Banigan and Mirny, 2020b). Alternately, multiple condensin monomers may be loaded at boundaries in random orientation, resulting in bi-directional extrusion, particularly when viewed at the cell population level (Banigan et al, 2020;Sebastian Jimenez et al, 2021).…”

DNA double-strand break end synapsis by DNA loop extrusion

“…4D,G ) and less frequently as gap-bridging LEFs ( Supplementary Fig. 4E,H ) [51]; the long-lived constraining LEFs provide a larger time window to attempt synapsis similar to stabilization of LEFs at BEs, as seen in the increased mean synapsis time ( Supplementary Fig. 4I ).…”

Structural changes in chromosomes driven by multiple condensin motors during mitosis

“…Both 6 the mechanisms might be operative in Xenopus eggs (Golfier et al 2020). It is possible that LE is mostly asymmetric during metaphase and symmetric during interphase (Banigan and Mirny 2020). In order to reconcile, at least partially, these seemingly opposing conclusions, we modified the LE scheme in order to investigate the consequences of symmetric LE on the P (s) as a function of s. As shown in Fig.…”