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Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly.

ABSTRACT: Gene expression in eukaryotes requires the effective separation of nuclear transcription and RNA processing from cytosolic translation¹. This separation is achieved by the nuclear envelope, which controls the exchange of macromolecules through nuclear pores². During mitosis, however, the nuclear envelope in animal and plant cells disassembles, allowing cytoplasmic and nuclear components to intermix³. When the nuclear envelope is reformed, cytoplasmic components are removed from the nucleus by receptor-mediated transport through nuclear pores². These pores have a size limit of 39 nanometres^4-7, which raises the question of how larger cytoplasmic molecules are cleared from the nucleus. Here we show in HeLa cells that large cytoplasmic components are displaced before nuclear envelope assembly by the movement of chromosomes to a dense cluster. This clustering occurs when chromosomes approach the poles of anaphase spindles, and is mediated by a microtubule-independent mechanism that involves the surfactant-like protein Ki-67. Ki-67 forms repulsive molecular brushes during the early stages of mitosis⁸, but during mitotic exit the brushes collapse and Ki-67 promotes chromosome clustering. We show that the exclusion of mature ribosomes from the nucleus after mitosis depends on Ki-67-regulated chromosome clustering. Thus, our study reveals that chromosome mechanics help to re-establish the compartmentalization of eukaryotic cells after open mitosis.

SUBMITTER: Cuylen-Haering S

PROVIDER: S-EPMC7666080 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly.

Cuylen-Haering Sara S Petrovic Mina M Hernandez-Armendariz Alberto A Schneider Maximilian W G MWG Samwer Matthias M Blaukopf Claudia C Holt Liam J LJ Gerlich Daniel W DW

Nature 20200902 7833

Gene expression in eukaryotes requires the effective separation of nuclear transcription and RNA processing from cytosolic translation1. This separation is achieved by the nuclear envelope, which controls the exchange of macromolecules through nuclear pores2. During mitosis, however, the nuclear envelope in animal and plant cells disassembles, allowing cytoplasmic and nuclear components to intermix3. When the nuclear envelope is reformed, cytoplasmic components a ...[more]

PMID: 32879492

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Project description:Nuclear lipids play roles in regulatory processes, such as signaling, transcriptional regulation, and DNA repair. In this report, we demonstrate that nuclear lipids may contribute to Ki-67-regulated chromosome integrity during mitosis. In COS-7 cells, nuclear lipids are enriched at the perichromosomal layer and excluded from intrachromosomal regions during early mitosis but are then detected in intrachromosomal regions during late mitosis, as revealed by TT-ExM (expansion microscopy with trypsin digestion and tyramide signal amplification), an improved expansion microscopy technique that enables high-sensitivity and super-resolution imaging of proteins, lipids, and nuclear DNA. The nuclear nonhistone protein Ki-67 acts as a surfactant to form a repulsive molecular brush around fully condensed sister chromatids in early mitosis, preventing the diffusion or penetration of nuclear lipids into intrachromosomal regions. Ki-67 is phosphorylated during mitosis by cyclin-dependent kinase 1 (CDK1), the best-known master regulator of the cell cycle. Both Ki-67 knockdown and reduced Ki-67 phosphorylation by CDK1 inhibitors allow nuclear lipids to penetrate chromosomal regions. Thus, both Ki-67 protein level and phosphorylation status during mitosis appear to influence the perichromosomal distribution of nuclear lipids. Ki-67 knockdown and CDK1 inhibition also lead to uneven chromosome disjunction between daughter cells, highlighting the critical role of this regulatory mechanism in ensuring accurate chromosome segregation. Given that Ki-67 has been proposed to promote chromosome individualization and establish chromosome-cytoplasmic compartmentalization during open mitosis in vertebrates, our results reveal that nuclear lipid enrichment at the perichromosomal layer enhances the ability of Ki-67 to form a protective perichromosomal barrier (chromosome envelope), which is critical for correct chromosome segregation and maintenance of genome integrity during mitosis.

Dataset Information

Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly.

Publications

Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly.

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