RT Journal Article
SR Electronic
T1 Mechanosensitive nuclear asymmetries define a bipolar spindle scaffold to ensure mitotic fidelity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 526939
DO 10.1101/526939
A1 Vanessa Nunes
A1 Margarida Dantas
A1 Domingos Castro
A1 Elisa Vitiello
A1 Irène Wang
A1 Nicolas Carpi
A1 Martial Balland
A1 Matthieu Piel
A1 Paulo Aguiar
A1 Helder Maiato
A1 Jorge G. Ferreira
YR 2019
UL http://biorxiv.org/content/early/2019/11/18/526939.abstract
AB 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 during prophase the centrosomes-nucleus axis reorients, so that centrosomes are positioned on the shortest nuclear axis at nuclear envelope (NE) breakdown. This centrosomes-nucleus configuration depends on mechanical cues generated by mitotic chromosome condensation on the prophase nucleus. We further show these mechanosensitive cues act through SUN1/2 and NudE+NudEL to enable the polarized loading of Dynein on the NE. 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.