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The mitotic protein NuMA plays a spindle-independent role in nuclear formation and mechanics

View ORCID ProfileAndrea Serra-Marques, Ronja Houtekamer, Dorine Hintzen, View ORCID ProfileJohn T. Canty, View ORCID ProfileAhmet Yildiz, View ORCID ProfileSophie Dumont
doi: https://doi.org/10.1101/2020.05.02.070680
Andrea Serra-Marques
1Department of Cell and Tissue Biology, University of California, San Francisco
2Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, USA
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  • For correspondence: sophie.dumont@ucsf.edu andrea.asmarques@gmail.com
Ronja Houtekamer
1Department of Cell and Tissue Biology, University of California, San Francisco
3Molecular Cancer Research, Center for Molecular Medicine, University Medical Center, Utrecht, the Netherlands
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Dorine Hintzen
1Department of Cell and Tissue Biology, University of California, San Francisco
4Department of Cell Biology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands
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John T. Canty
5Biophysics Graduate Group, University of California, Berkeley, USA
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Ahmet Yildiz
5Biophysics Graduate Group, University of California, Berkeley, USA
6Department of Molecular and Cellular Biology, University of California, Berkeley, USA
7Department of Physics, University of California, Berkeley, USA
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Sophie Dumont
1Department of Cell and Tissue Biology, University of California, San Francisco
2Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, USA
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  • For correspondence: sophie.dumont@ucsf.edu andrea.asmarques@gmail.com
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Abstract

Eukaryotic cells typically form a single, round nucleus after mitosis, and failures to do so can compromise genomic integrity. How mammalian cells form such a nucleus remains incompletely understood. NuMA is a spindle protein whose disruption results in nuclear fragmentation. What role NuMA plays in nuclear integrity, or whether its perceived role stems from its spindle function, is unclear. Here, we use live imaging to demonstrate that NuMA plays a spindle-independent role in forming a single, round nucleus. NuMA keeps the decondensing chromosome mass compact at mitotic exit, and promotes a mechanically robust nucleus. NuMA’s C-terminus binds DNA in vitro and chromosomes in interphase, while its coiled-coil acts as a regulatory and structural hub: it prevents NuMA from binding chromosomes at mitosis, regulates its nuclear mobility and is essential for nuclear formation. Thus, NuMA plays a long-range structural role in building and maintaining an intact nucleus, as it does for the spindle, playing a protective role over the cell cycle.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 03, 2020.
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The mitotic protein NuMA plays a spindle-independent role in nuclear formation and mechanics
Andrea Serra-Marques, Ronja Houtekamer, Dorine Hintzen, John T. Canty, Ahmet Yildiz, Sophie Dumont
bioRxiv 2020.05.02.070680; doi: https://doi.org/10.1101/2020.05.02.070680
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The mitotic protein NuMA plays a spindle-independent role in nuclear formation and mechanics
Andrea Serra-Marques, Ronja Houtekamer, Dorine Hintzen, John T. Canty, Ahmet Yildiz, Sophie Dumont
bioRxiv 2020.05.02.070680; doi: https://doi.org/10.1101/2020.05.02.070680

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