Real-time imaging of DNA loop extrusion by condensin

Ganji, Mahipal; Shaltiël, Indra A.; Bisht, S.; Kim, Eugene; Kalichava, Ana; Haering, Christian H.; Dekker, Cees

doi:10.1126/science.aar7831

Cited by 732 publications

(1,031 citation statements)

References 30 publications

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“…Even without any cooperative interaction between SMCs, “loop-extrusion” dynamics could drive condensin accumulation at the bases of chromatin loop domains while compacting chromosomes (Alipour and Marko, 2012, Goloborodko et al, 2016b, Goloborodko et al, 2016a). Single-molecule experiments have indeed observed DNA translocation (Terakawa et al, 2017) and loop-extrusion (Ganji et al, 2018) dynamics for yeast condensin, supporting this model. A possible molecular mechanism underlying loop extrusion by condensin which is consistent with the observations of (Ganji et al, 2018) has been presented in (Lawrimore et al, 2017).…”

Section: Discussionmentioning

confidence: 57%

“…Single-molecule experiments have indeed observed DNA translocation (Terakawa et al, 2017) and loop-extrusion (Ganji et al, 2018) dynamics for yeast condensin, supporting this model. A possible molecular mechanism underlying loop extrusion by condensin which is consistent with the observations of (Ganji et al, 2018) has been presented in (Lawrimore et al, 2017). …”

Section: Discussionmentioning

confidence: 57%

“…A conceivable mechanism for lengthwise compaction is progressive “extrusion” of chromatin loops by condensins (Marko, 2011, Alipour and Marko, 2012, Marko, 2009, Nasmyth, 2001, Goloborodko et al, 2016a, Goloborodko et al, 2016b, Gibcus et al, 2018, Ganji et al, 2018). In such a model, condensin II would act to push chromatin to the exterior of the chromosome, perhaps in concert with condensin-associated factors such as the chromokinesin KIF4, (Samejima et al, 2012), with crowding of chromatin loops providing a thermodynamic drive for topo II to remove interlocks between different chromatids and chromosome.…”

Section: Discussionmentioning

confidence: 99%

“…Despite direct observation of loop-extrusion dynamics by yeast cohesin (Ganji et al, 2018), it remains conceivable that simpler chromatin-looping mechanisms may dominate metaphase chromosome self-organization (Cheng et al, 2015, Marko and Siggia, 1997). However, whatever the detailed molecular mechanisms, our observations are in excellent accord with the general model that condensin and topoisomerase II work together to segregate chromosomes, with condensin compacting chromatin and topo II changing chromatin topology (Hirano, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

et al. 2018

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During cell division, chromosomes must be folded into their compact mitotic form to ensure their segregation. This process is thought to be largely controlled by the action of condensin SMC protein complexes on chromatin fibers. However, how condensins organize metaphase chromosomes is not understood. We have combined micromanipulation of single human mitotic chromosomes, sub-nanonewton force measurement, siRNA interference of condensin subunit expression, and fluorescence microscopy, to analyze the role of condensin in large-scale chromosome organization. Condensin depletion leads to a dramatic (~ 10-fold) reduction in chromosome elastic stiffness relative to the native, non-depleted case. We also find that prolonged metaphase stalling of cells leads to overloading of chromosomes with condensin, with abnormally high chromosome stiffness. These results demonstrate that condensin is a main element controlling the stiffness of mitotic chromosomes. Isolated, slightly stretched chromosomes display a discontinuous condensing staining pattern, suggesting that condensins organize mitotic chromosomes by forming isolated compaction centers that do not form a continuous scaffold.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

et al. 2018

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“…Recent in vitro single molecule observations have also opened the possibility that SMC complexes function as DNA loop extrusion machines. Purified budding yeast condensin promotes the formation and enlargement of DNA loops in an ATP-dependent manner [81]. In a different experimental setting, condensin has also been shown to translocate along DNA unidirectionally, which requires its intact ATPase [82].…”

Section: Intrachromosomal Interactions: Another Open Questionmentioning

confidence: 99%

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

Murayama

2018

Nucleus

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Cohesin is a ring-shaped, multi-subunit ATPase assembly that is fundamental to the spatiotemporal organization of chromosomes. The ring establishes a variety of chromosomal structures including sister chromatid cohesion and chromatin loops. At the core of the ring is a pair of highly conserved SMC (Structural Maintenance of Chromosomes) proteins, which are closed by the flexible kleisin subunit. In common with other essential SMC complexes including condensin and the SMC5-6 complex, cohesin encircles DNA inside its cavity, with the aid of HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A and TOR) repeat auxiliary proteins. Through this topological embrace, cohesin is thought to establish a series of intra- and interchromosomal interactions by tethering more than one DNA molecule. Recent progress in biochemical reconstitution of cohesin provides molecular insights into how this ring complex topologically binds and mediates DNA-DNA interactions. Here, I review these studies and discuss how cohesin mediates such chromosome interactions.

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Conformation Dynamics of Single Polymer Strands in Solution

Bae

Bang

et al. 2022

Advanced Materials

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structures. For example, intrinsically disordered proteins, which account for one-third of the proteins in the human proteome, do not adopt a standardized 3D structure, and their spontaneous interconversion between unfolded states is crucial in dynamic biological processes. [4] In addition, various synthetic polymers, which are highly regulated by complex molecular interactions and the resulting conformational changes, form a variety of highorder structures via the self-structuring of individual molecules. [5][6][7][8] Thus, it is important to understand the intrinsic structural diversity and dynamic behaviors of individual macromolecules at the single-chain level.Over the last few decades, the conformation and dynamics of a single chain have been widely studied both theoretically and experimentally. Theoretical and computational modeling of single-chain dynamics in ideal solutions are well established in the field of polymer physics. [9][10][11][12] Moreover, enhanced sampling simulation techniques can efficiently locate candidates for energetically stable structures and calculate the free energy differences between their distinct states. [13][14][15] Nonetheless, it is still challenging to understand realistic single-chain behaviors using computational methods, as it is not trivial to simulate ion-solute interactions, crowding, or confinement in polymer solutions. [16][17][18] Furthermore, it is not rare to find a Conformational changes in macromolecules significantly affect their functions and assembly into high-level structures. Despite advances in theoretical and experimental studies, investigations into the intrinsic conformational variations and dynamic motions of single macromolecules remain challenging. Here, liquid-phase transmission electron microscopy enables the real-time tracking of single-chain polymers. Imaging linear polymers, synthetically dendronized with conjugated aromatic groups, in organic solvent confined within graphene liquid cells, directly exhibits chain-resolved conformational dynamics of individual semiflexible polymers. These experimental and theoretical analyses reveal that the dynamic conformational transitions of the single-chain polymer originate from the degree of intrachain interactions. In situ observations also show that such dynamics of the single-chain polymer are significantly affected by environmental factors, including surfaces and interfaces.

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Real-time imaging of DNA loop extrusion by condensin

Cited by 732 publications

References 30 publications

Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

Conformation Dynamics of Single Polymer Strands in Solution

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