Can pseudotopological models for SMC-driven DNA loop extrusion explain the traversal of physical roadblocks bigger than the SMC ring size?

Abstract

DNA loop extrusion by structural-maintenance-of-chromosome (SMC) complexes has emerged as a primary organizing principle for chromosomes. The mechanism by which SMC motor proteins extrude DNA loops is still unresolved and much debated. The ring-like structure of SMC complexes prompted multiple models where the extruded DNA is topologically or pseudotopologically entrapped within the ring during loop extrusion. However, recent experiments showed the passage of roadblocks much bigger than the SMC ring size, suggesting a nontopological mechanism. Recently, attempts were made to reconcile the observed passage of large roadblocks with a pseudotopological mechanism. Here we examine the predictions of these pseudotopological models, and find that they are not consistent with some experimental data on SMC roadblock encounters. Particularly, these models predict the formation of two loops and that roadblocks will reside near the stem of the loop upon encounter - both in contrast to experimental observations. Overall, the experimental data reinforce the notion of a nontopological mechanism for extrusion of DNA.

SMC Complexes Can Traverse Physical Roadblocks Bigger Than Their Ring Size

“…Prompted by our preprint data, these authors attempted to account for the passage of large obstacles within their model (SI Figure S25 in Shaltiel et al, 2022, andSI Figure S6 in Nomidis et al, 2022). However, this alternative interpretation of our data makes a number of predictions that are not supported by the experimental results (Pradhan et al, 2022a). Specifically, when the SMC encounters a large roadblock, these models predict the appearance of two loops, not one, since the roadblock-with its size that cannot pass the ring structure-obstructs the merging of the two preformed loops postulated in the models, and hence leads to the formation of a second loop.…”