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Mechanosensitive Nuclear Asymmetries Define a Bipolar Spindle Scaffold to Ensure Mitotic Fidelity

44 Pages Posted: 9 Aug 2019 Publication Status: Review Complete

See all articles by Vanessa Nunes

Vanessa Nunes

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

Margarida Dantas

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

Elisa Vitiello

Université Joseph Fourier

Irène Wang

Université Joseph Fourier

Nicolas Carpi

PSL Research University - Institut Curie

Martial Balland

University of Grenoble

Matthieu Piel

PSL Research University - UMR144; PSL Research University - Institut Curie

Paulo Aguiar

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

Helder Maiato

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

Jorge Ferreira

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

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Abstract

During prophase, centrosomes need to separate and position to correctly assemble the mitotic spindle. This process occurs through the action of molecular motors, cytoskeletal networks and the nucleus. How the combined activity of these different components is spatiotemporally regulated to ensure efficient spindle assembly remains unclear. Here, we show that mitotic rounding during prophase facilitates the reorientation of the centrosomes-nucleus axis, so that centrosomes position on the shortest nuclear axis at nuclear envelope (NE) breakdown. This centrosome configuration depends on mitotic chromosome condensation that creates a mechanosensitive environment on the prophase nucleus, essential for the polarized loading of Dynein on the NE. This occurs independently of its known NE adaptors. Finally, we observe this centrosome configuration favors the establishment of an initial bipolar spindle scaffold, facilitating chromosome capture and accurate segregation, without compromising division plane orientation. We propose that chromosome segregation fidelity depends on the mechanical properties of the prophase nucleus that facilitate spindle assembly by regulating NE-Dynein localization.

Keywords: Mitosis, Centrosome, nucleus, Chromatin condensation, chromosome, Dynein, Arp2/3, Mitotic spindle

Suggested Citation

Nunes, Vanessa and Dantas, Margarida and Vitiello, Elisa and Wang, Irène and Carpi, Nicolas and Balland, Martial and Piel, Matthieu and Aguiar, Paulo and Maiato, Helder and Ferreira, Jorge, Mechanosensitive Nuclear Asymmetries Define a Bipolar Spindle Scaffold to Ensure Mitotic Fidelity (August 9, 2019). Available at SSRN: https://ssrn.com/abstract=3434727 or http://dx.doi.org/10.2139/ssrn.3434727
This version of the paper has not been formally peer reviewed.

Vanessa Nunes

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

Rua Alfredo Allen, 208
Porto
Portugal

Margarida Dantas

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

Rua Alfredo Allen, 208
Porto
Portugal

Elisa Vitiello

Université Joseph Fourier ( email )

B.P. 53
Cedex 9
Grenoble, 38041
France

Irène Wang

Université Joseph Fourier ( email )

B.P. 53
Cedex 9
Grenoble, 38041
France

Nicolas Carpi

PSL Research University - Institut Curie

Martial Balland

University of Grenoble ( email )

B.P. 53
Cedex 9
Grenoble, 38041
France

Matthieu Piel

PSL Research University - UMR144 ( email )

PSL Research University - Institut Curie ( email )

Paris, CNRS UMR14
France

Paulo Aguiar

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

Rua Alfredo Allen, 208
Porto
Portugal

Helder Maiato

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

Rua Alfredo Allen, 208
Porto
Portugal

Jorge Ferreira (Contact Author)

Universidade do Porto - Instituto de Investigação e Inovação em Saúde - i3S

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