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1.
J Cell Biol ; 223(1)2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976091

RESUMO

Eukaryotic chromosomes compact during mitosis into elongated cylinders-and not the spherical globules expected of self-attracting long flexible polymers. This process is mainly driven by condensin-like proteins. Here, we present Brownian-dynamic simulations involving two types of such proteins with different activities. One, which we refer to as looping condensins, anchors long-lived chromatin loops to create bottlebrush structures. The second, referred to as bridging condensins, forms multivalent bridges between distant parts of these loops. We show that binding of bridging condensins leads to the formation of shorter and stiffer mitotic-like cylinders without requiring any additional energy input. These cylinders have several features matching experimental observations. For instance, the axial condensin backbone breaks up into clusters as found by microscopy, and cylinder elasticity qualitatively matches that seen in chromosome pulling experiments. Additionally, simulating global condensin depletion or local faulty condensin loading gives phenotypes seen experimentally and points to a mechanistic basis for the structure of common fragile sites in mitotic chromosomes.


Assuntos
Adenosina Trifosfatases , Cromossomos , Proteínas de Ligação a DNA , Complexos Multiproteicos , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Cromatina/genética , Cromossomos/genética , Cromossomos/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Mitose , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo
2.
Soft Matter ; 20(1): 71-78, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37877330

RESUMO

Knots are deeply entangled with every branch of science. One of the biggest open challenges in knot theory is to formalise a knot invariant that can unambiguously and efficiently distinguish any two knotted curves. Additionally, the conjecture that the geometrical embedding of a curve encodes information on its underlying topology is, albeit physically intuitive, far from proven. Here we attempt to tackle both these outstanding challenges by proposing a neural network (NN) approach that takes as input a geometric representation of a knotted curve and tries to make predictions of the curve's topology. Intriguingly, we discover that NNs trained with a so-called geometrical "local writhe" representation of a knot can distinguish curves that share one or many topological invariants and knot polynomials, such as mutant and composite knots, and can thus classify knotted curves more precisely than some knot polynomials. Additionally, we also show that our approach can be scaled up to classify all prime knots up to 10-crossings with more than 95% accuracy. Finally, we show that our NNs can also be trained to solve knot localisation problems on open and closed curves. Our main discovery is that the pattern of "local writhe" is a potentially unique geometric signature of the underlying topology of a curve. We hope that our results will suggest new methods for quantifying generic entanglements in soft matter and even inform new topological invariants.

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