The condensin holocomplex cycles dynamically between open and collapsed states

Ryu, Je-Kyung; Katan, Allard J.; Sluis, Eli O. van der; Wisse, Thomas; Groot, Ralph de; Haering, Christian H.; Dekker, Cees

doi:10.1038/s41594-020-0508-3

Cited by 77 publications

(155 citation statements)

References 56 publications

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“…In order to determine the persistence length of the connecting coiled coil for our simulations, we sampled conformational states of cohesin alone as it transitions multiple times between slipping and gripping states. We found that at the persistence length 66 = 50 nm our simulations match the experimentally observed head-to-hinge distance distribution available for the condensin complex (Ryu et al, 2020b). A smaller persistence length for condensin's coiled coil of 66 = 4 nm was previously reported (Eeftens et al, 2016), which included the flexible elbow region that is considered separately in our simulations.…”

Section: Cohesin Modelsupporting

confidence: 84%

A Brownian ratchet model for DNA loop extrusion by the cohesin complex

Higashi

Tang

Pobegalov

et al. 2021

Preprint

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The cohesin complex topologically encircles DNA to promote sister chromatid cohesion. Alternatively cohesin extrudes DNA loops, thought to reflect chromatin domain formation. Here, we propose a structure-based model explaining both activities, supported by biochemical experiments. ATP and DNA binding to cohesin promote conformational changes that guide DNA through a kleisin gate into a DNA gripping state. Two HEAT-repeat DNA binding modules, associated with cohesins heads and hinge, are now juxtaposed. ATP hydrolysis disassembles the gripping state, allowing unidirectional hinge module movement to complete topological DNA entry. Without initial kleisin gate passage, biased hinge module motion during gripping state resolution creates a Brownian ratchet that drives loop extrusion. Molecular-mechanical simulations of gripping state formation and resolution cycles recapitulate experimentally observed DNA loop extrusion characteristics. Our model extends to asymmetric and symmetric loop extrusion, as well as z-loop formation. Loop extrusion by biased Brownian fluctuations has important implications for chromosomal cohesin function.

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Section: Cohesin Modelsupporting

confidence: 84%

A Brownian ratchet model for DNA loop extrusion by the cohesin complex

Higashi

Tang

Pobegalov

et al. 2021

Preprint

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“…S1). A recent AFM study (Ryu et al, 2020) showed large reversible hinge-to-globular domain motions of 22 ± 13 nm. Regarding the mechanochemical ATP hydrolysis cycle that drives the DNA extrusion, this recent AFM study of yeast condensin as well as a cryo-EM study of human cohesin demonstrated that ATP binding induces large conformational changes of the hinge domain (Higashi et al, 2020; Ryu et al, 2020; Shi et al, 2020).…”

Section: Introductionmentioning

confidence: 97%

“…A recent AFM study (Ryu et al, 2020) showed large reversible hinge-to-globular domain motions of 22 ± 13 nm. Regarding the mechanochemical ATP hydrolysis cycle that drives the DNA extrusion, this recent AFM study of yeast condensin as well as a cryo-EM study of human cohesin demonstrated that ATP binding induces large conformational changes of the hinge domain (Higashi et al, 2020; Ryu et al, 2020; Shi et al, 2020). In attempts to measure condensin-mediated DNA extrusion step sizes, previous single-molecule magnetic tweezers (MT) studies showed significantly varying values, ranging from ~80 nm for Xenopus condensin I (Strick et al, 2004) to ~200 nm for yeast condensin (Eeftens et al, 2017) – significantly larger than the 50 nm condensin complex size that one intuitively would expect.…”

Section: Introductionmentioning

confidence: 97%

“…Structural studies of condensin have suggested various sizeable conformational changes of the protein complex that are potentially associated with the loop-extrusion stepping (Hassler et al, 2018; Lee et al, 2020; Ryu et al, 2020; Yoshimura et al, 2002). Condensin consists of a ring formed by two 50 nm long antiparallel coiled-coil SMC arms that are mutually engaged by a hinge domain, and, at the opposite site of the ring, a globular domain consisting of two ATPase heads of the SMCs, the Brn1 kleisin, and two HEAT-repeat domains, Ycs4 and Ycg1 (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Condensin extrudes DNA loops in steps up to hundreds of base pairs that are generated by ATP binding events

Ryu

Rah

Janissen

et al. 2020

Preprint

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The condensin SMC protein complex organizes chromosomal structure by extruding loops of DNA. Its ATP-dependent motor mechanism remains unclear but likely involves steps associated with large conformational changes within the ~50 nm protein complex. Here, using magnetic tweezers, we resolve single steps in loop extrusion by individual yeast condensins. Step sizes range between 20-45 nm at forces of 1.0-0.2 pN, respectively, comparable to the complex size. The large steps show that condensin reels in DNA in very sizeable amounts, up to ~600 bp per extrusion step, consistent with the non-stretched DNA polymer at these low forces. Using ATP-binding-impaired and ATP-hydrolysis-deficient mutants, we find that ATP binding is the primary step-generating stage underlying DNA loop extrusion. We discuss the findings in terms of a scrunching model where a stepwise DNA loop extrusion is generated by an ATP-binding-induced engagement of the hinge and the globular domain of the SMC complex.

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“…Members of the structural maintenance of chromosome (SMC) protein family such as condensin, cohesin, and the Smc5/6 complex are key proteins for the spatial and temporal organization of chromosomes (1)(2)(3)(4). Recent in vitro experiments visualized real-time DNA loop extrusion mediated by condensin and cohesin (5)(6)(7)(8). While loop extrusion by SMC proteins constitutes a fundamental building block in the organization of chromosomes, other factors may also contribute.…”

Section: Introductionmentioning

confidence: 99%

Bridging-induced phase separation induced by cohesin SMC protein complexes

et al. 2021

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Structural maintenance of chromosome (SMC) protein complexes are able to extrude DNA loops. While loop extrusion constitutes a fundamental building block of chromosomes, other factors may be equally important. Here, we show that yeast cohesin exhibits pronounced clustering on DNA, with all the hallmarks of biomolecular condensation. DNA-cohesin clusters exhibit liquid-like behavior, showing fusion of clusters, rapid fluorescence recovery after photobleaching and exchange of cohesin with the environment. Strikingly, the in vitro clustering is DNA length dependent, as cohesin forms clusters only on DNA exceeding 3 kilo–base pairs. We discuss how bridging-induced phase separation, a previously unobserved type of biological condensation, can explain the DNA-cohesin clustering through DNA-cohesin-DNA bridges. We confirm that, in yeast cells in vivo, a fraction of cohesin associates with chromatin in a manner consistent with bridging-induced phase separation. Biomolecular condensation by SMC proteins constitutes a new basic principle by which SMC complexes direct genome organization.

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The condensin holocomplex cycles dynamically between open and collapsed states

Cited by 77 publications

References 56 publications

A Brownian ratchet model for DNA loop extrusion by the cohesin complex

A Brownian ratchet model for DNA loop extrusion by the cohesin complex

Condensin extrudes DNA loops in steps up to hundreds of base pairs that are generated by ATP binding events

Bridging-induced phase separation induced by cohesin SMC protein complexes

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