Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin

Sacristan, Carlos; Samejima, Kumiko; Ruiz, Lorena Andrade; Deb, Moonmoon; Lambers, Maaike L.A.; Buckle, Adam; Brackley, Chris A.; Robertson, Daniel; Hori, Tetsuya; Webb, Shaun; Kiewisz, Robert; Bepler, Tristan; van Kwawegen, Eloïse; Risteski, Patrik; Vukušić, Kruno; Tolić, Iva M.; Müller-Reichert, Thomas; Fukagawa, Tatsuo; Gilbert, Nick; Marenduzzo, Davide; Earnshaw, William C.; Kops, Geert J.P.L.

doi:10.1016/j.cell.2024.04.014

Cited by 7 publications

References 87 publications

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Vertebrate centromere architecture: from chromatin threads to functional structures

Andrade Ruiz,

Kops,

Sacristan

2024

Chromosoma

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Centromeres are chromatin structures specialized in sister chromatid cohesion, kinetochore assembly, and microtubule attachment during chromosome segregation. The regional centromere of vertebrates consists of long regions of highly repetitive sequences occupied by the Histone H3 variant CENP-A, and which are flanked by pericentromeres. The three-dimensional organization of centromeric chromatin is paramount for its functionality and its ability to withstand spindle forces. Alongside CENP-A, key contributors to the folding of this structure include components of the Constitutive Centromere-Associated Network (CCAN), the protein CENP-B, and condensin and cohesin complexes. Despite its importance, the intricate architecture of the regional centromere of vertebrates remains largely unknown. Recent advancements in long-read sequencing, super-resolution and cryo-electron microscopy, and chromosome conformation capture techniques have significantly improved our understanding of this structure at various levels, from the linear arrangement of centromeric sequences and their epigenetic landscape to their higher-order compaction. In this review, we discuss the latest insights on centromere organization and place them in the context of recent findings describing a bipartite higher-order organization of the centromere.

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Vertebrate centromere architecture: from chromatin threads to functional structures

Andrade Ruiz,

Kops,

Sacristan

2024

Chromosoma

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Force generation and resistance in human mitosis

Caldwell,

Clement,

Wuite

2024

Biophys Rev

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Since the first observations of chromosome segregation over 150 years ago, efforts to observe the forces that drive mitosis have evolved alongside advances in microscopy. The mitotic spindle acts as the major generator of force through the highly regulated polymerization and depolymerization of microtubules as well as associated motor proteins. Centromeric chromatin, along with associated proteins including cohesin and condensin, is organized to resist these forces and ensure accurate chromosome segregation. Microtubules and centromeric chromatin join at the kinetochore, a complex protein superstructure. Ongoing research into the forces generated at the kinetochore-microtubule interface has resulted in a range of estimates for forces necessary to separate chromosomes, from tens to hundreds of piconewtons. Still, the exact magnitude and regulation of these forces remain areas of continuing investigation. Determining the precise forces involved in chromosome segregation is hindered by limitations of current measurement techniques, but advances such as optical tweezers combined with fluorescence microscopy are promising for future research.

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Chromosome segregation: Brushing up on centromeres

Bloom

2024

Current Biology

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Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin

Cited by 7 publications

References 87 publications

Vertebrate centromere architecture: from chromatin threads to functional structures

Vertebrate centromere architecture: from chromatin threads to functional structures

Force generation and resistance in human mitosis

Chromosome segregation: Brushing up on centromeres

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