DNA-segment-capture model for loop extrusion by structural maintenance of chromosome (SMC) protein complexes

Abstract

Cells possess remarkable control of the folding and entanglement topology of very long and flexible chromosomal DNA molecules. It is thought that structural maintenance of chromosome (SMC) protein complexes play a crucial role in this, by organizing long DNAs into series of loops.Recent experimental data suggest that SMC complexes are able to translocate on DNA, as well as pull out lengths of DNA via a 'loop extrusion' process. We describe a Brownian loop-captureratchet model for translocation and loop extrusion based on known structural, catalytic, and DNA-binding properties of the Bacillus subtilis SMC complex. Our model provides an example of a new class of molecular motor where large conformational fluctuations of the motor 'track' -in this case DNA -are involved in the basic translocation process. Quantitative analysis of our model leads to a series of predictions for the motor properties of SMC complexes, most strikingly a strong dependence of SMC translocation velocity on tension in the DNA track that it is moving along.

Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures

“…Loop extrusion has emerged as a vital mechanism underlying organization of chromosomes. SMC complexes (cohesin and condesnsins) can exert pN forces and are the prime candidates for driving the loop extrusion activity [26,27,[61][62][63][64]. In our model, extrusion of loops generates interloop repulsion that stretches the backbone; thus, loop extrusion may effectively control n, m, and α to drive chromosome compaction, and consequently, disentanglement in presence of Topo II.…”

A tethered-inchworm model of SMC DNA translocation

“…It has been proposed that the kleisin-HAWK topological binding pocket may serve as the anchor 26 , which would leave the comparatively simple hinge domain to serve as a motor. In one proposed model the SMC arms and hinge act as a DNA pump 26,27 . In this model, DNA loops are loaded into the ring formed by the SMC arms and ATP driven conformational changes close the ring, driving the loop into a smaller chamber formed by the kleisin and SMC heads where it combines with a larger loop.…”

Are SMC Complexes Loop Extruding Factors? Linking Theory With Fact

“…A stepwise action for SMC translocation argues against the continuous type of translocation seen in DNA helicases or polymerases. The combined characteristics of translocation along DNA have suggested several different models for how SMC complexes could act as LEF machines, including “walking,” “rock climbing,” or “loop capture ratchet”/“scrunching” mechanisms (Figure b–d). The “walking” model requires three distinct DNA binding sites within the complex, at the hinge and proximal to each of the SMC head domains, to coordinate translocation along one section of DNA while maintaining a linkage with a second (Figure b).…”

“…Finally, the “ratchet/scrunching” model is proposed to work by one or two SMC complexes opening their coiled coils (following ATP binding) before “snapping back” of the coiled coils after ATP hydrolysis and ADP displacement (Figure d). It is proposed that the process of snapping back of the coiled coils forces DNA, interacting with the hinge and head following ATP binding, into a lower compartment, formed by the interface between the SMC dimer and the bridging kleisin/non‐SMC subcomplex . A biophysical model based on this process has recently described this hypothetical mechanism in detail …”

“…It is proposed that the process of snapping back of the coiled coils forces DNA, interacting with the hinge and head following ATP binding, into a lower compartment, formed by the interface between the SMC dimer and the bridging kleisin/non‐SMC subcomplex . A biophysical model based on this process has recently described this hypothetical mechanism in detail …”