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NuMA interaction with chromatin is vital for proper chromosome decondensation at the mitotic exit

Rajeevan, A and Keshri, R and Kapoor, S and Kotak, S (2020) NuMA interaction with chromatin is vital for proper chromosome decondensation at the mitotic exit. In: Molecular Biology of the Cell, 31 (22). pp. 2437-2451.

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Official URL: https://doi.org/10.1091/MBC.E20-06-0415


NuMA is an abundant long coiled-coil protein that plays a prominent role in spindle organization during mitosis. In interphase, NuMA is localized to the nucleus and hypothesized to control gene expression and chromatin organization. However, because of the prominent mitotic phenotype upon NuMA loss, its precise function in the interphase nucleus remains elusive. Here, we report that NuMA is associated with chromatin in interphase and prophase but released upon nuclear envelope breakdown (NEBD) by the action of Cdk1. We uncover that NuMA directly interacts with DNA via evolutionarily conserved sequences in its C-terminus. Notably, the expression of the DNA-binding–deficient mutant of NuMA affects chromatin decondensation at the mitotic exit, and nuclear shape in interphase. We show that the nuclear shape defects observed upon mutant NuMA expression are due to its potential to polymerize into higher-order fibrillar structures. Overall, this work establishes the spindle-independent function of NuMA in choreographing proper chromatin decompaction and nuclear shape by directly associating with the DNA. © 2020 American Society for Cell Biology. All rights reserved.

Item Type: Journal Article
Publication: Molecular Biology of the Cell
Publisher: American Society for Cell Biology
Additional Information: The copyright for this article belongs to The Authors.
Keywords: arginine; cyclin B1; cyclin dependent kinase 1; DNA; double stranded DNA; lamin B; lysine; mutant protein; nuclear mitotic apparatus protein; plasmid DNA; protein; unclassified drug; cell cycle protein; cell nucleus antigen; chromosome decondensation factors; cyclin dependent kinase 1; DNA; nonhistone protein; nuclear matrix protein; nuclear protein; NUMA1 protein, human, Article; carboxy terminal sequence; cell nucleus matrix; cell nucleus membrane; chromatin; chromatin condensation; chromosome; conserved sequence; DNA binding; genetic association; human; human cell; interphase; mitosis; nuclear shape; priority journal; prophase; protein analysis; protein DNA binding; protein DNA interaction; protein expression; protein phosphorylation; protein structure; spindle cell; cell cycle; cell nucleus; chromatin; chromosome; genetics; HeLa cell line; metabolism; mitosis; nuclear division; physiology; spindle apparatus, Antigens, Nuclear; CDC2 Protein Kinase; Cell Cycle; Cell Cycle Proteins; Cell Nucleus; Cell Nucleus Division; Chromatin; Chromosomal Proteins, Non-Histone; Chromosomes; DNA; HeLa Cells; Humans; Mitosis; Nuclear Matrix-Associated Proteins; Nuclear Proteins; Spindle Apparatus
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 12 Jan 2023 08:42
Last Modified: 12 Jan 2023 08:42
URI: https://eprints.iisc.ac.in/id/eprint/79056

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