Centripetal nuclear shape fluctuations associate with chromatin condensation in early prophase

Introini, Viola; Kidiyoor, Gururaj Rao; Porcella, G.; Cicuta, Pietro; Lagomarsino, Marco Cosentino

doi:10.1038/s42003-023-05074-9

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…During this brief period of the cell cycle, all nuclear components, such as nuclear membranes, NPCs, and the nuclear lamina must be dramatically reorganized. The disassembly of all these components, in collaboration with chromatin condensation, likely results in modifications of the mechanical properties of the nucleus [ 56 , 160 ], which ultimately culminates in its disassembly during NEB ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, condensed chromosomes display an increased stiffness when compared to interphase chromosomes [ 34 , 158 , 159 ] , , which also correlates with the higher nuclear tension observed during late G2/early mitosis [ 10 ]. Because this condensing chromatin is tethered to the NE at discrete sites, it can generate local inward pulling forces on the NE, which are sufficient to cause centripetal shape fluctuations [ 160 ]. Interestingly, impairment of chromatin condensation at the onset of mitosis due to treatment with trichostatin A (TSA), a pan-histone deacetylase inhibitor, greatly reduces these fluctuations, suggesting that chromosome condensation is an active mechanical component in this process.…”

Section: Chromatinmentioning

confidence: 99%

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Mechanobiology of the nucleus during the G2-M transition

Lima,

Ferreira

2024

Nucleus

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Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged as a regulator of cellular response to mechanical stimuli. Cell cycle progression is regulated by cyclin-CDK complexes. Recent studies demonstrated these biochemical pathways are influenced by mechanical signals, highlighting the interdependence of cellular mechanics and cell cycle regulation. In particular, the transition from G2 to mitosis (G2-M) shows significant changes in nuclear structure and organization, ranging from nuclear pore complex (NPC) and nuclear lamina disassembly to chromosome condensation. The remodeling of these mechanically active nuclear components indicates that mitotic entry is particularly sensitive to forces. Here, we address how mechanical forces crosstalk with the nucleus to determine the timing and efficiency of the G2-M transition. Finally, we discuss how the deregulation of nuclear mechanics has consequences for mitosis.

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Section: Discussionmentioning

confidence: 99%

Section: Chromatinmentioning

confidence: 99%

Mechanobiology of the nucleus during the G2-M transition

Lima,

Ferreira

2024

Nucleus

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Centripetal nuclear shape fluctuations associate with chromatin condensation in early prophase

et al. 2023

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The nucleus plays a central role in several key cellular processes, including chromosome organisation, DNA replication and gene transcription. Recent work suggests an association between nuclear mechanics and cell-cycle progression, but many aspects of this connection remain unexplored. Here, by monitoring nuclear shape fluctuations at different cell cycle stages, we uncover increasing inward fluctuations in late G2 and in early prophase, which are initially transient, but develop into instabilities when approaching the nuclear-envelope breakdown. We demonstrate that such deformations correlate with chromatin condensation by perturbing both the chromatin and the cytoskeletal structures. We propose that the contrasting forces between an extensile stress and centripetal pulling from chromatin condensation could mechanically link chromosome condensation with nuclear-envelope breakdown, two main nuclear processes occurring during mitosis.

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Chromatin phase separation and nuclear shape fluctuations are correlated in a polymer model of the nucleus

Attar,

Paturej,

Banigan

et al. 2024

Nucleus

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Abnormal cell nuclear shapes are hallmarks of diseases, including progeria, muscular dystrophy, and many cancers. Experiments have shown that disruption of heterochromatin and increases in euchromatin lead to nuclear deformations, such as blebs and ruptures. However, the physical mechanisms through which chromatin governs nuclear shape are poorly understood. To investigate how heterochromatin and euchromatin might govern nuclear morphology, we studied chromatin microphase separation in a composite coarse-grained polymer and elastic shell simulation model. By varying chromatin density, heterochromatin composition, and heterochromatin-lamina interactions, we show how the chromatin phase organization may perturb nuclear shape. Increasing chromatin density stabilizes the lamina against large fluctuations. However, increasing heterochromatin levels or heterochromatin-lamina interactions enhances nuclear shape fluctuations by a “wetting”-like interaction. In contrast, fluctuations are insensitive to heterochromatin’s internal structure. Our simulations suggest that peripheral heterochromatin accumulation could perturb nuclear morphology, while nuclear shape stabilization likely occurs through mechanisms other than chromatin microphase organization.

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Centripetal nuclear shape fluctuations associate with chromatin condensation in early prophase

Cited by 3 publications

References 51 publications

Mechanobiology of the nucleus during the G2-M transition

Mechanobiology of the nucleus during the G2-M transition

Centripetal nuclear shape fluctuations associate with chromatin condensation in early prophase

Chromatin phase separation and nuclear shape fluctuations are correlated in a polymer model of the nucleus

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