Prophase-specific perinuclear actin coordinates centrosome separation and positioning to ensure accurate chromosome segregation

Stiff, Tom, Echegaray-Iturra, Fabio R, Pink, Harry J, Herbert, Alex, Reyes-Aldasoro, Constantino Carlos and Hochegger, Helfrid (2020) Prophase-specific perinuclear actin coordinates centrosome separation and positioning to ensure accurate chromosome segregation. Cell Reports, 31 (8). a107681. ISSN 2211-1247

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Abstract

Centrosome separation in late G2/ early prophase requires precise spatial coordination that is determined by a balance of forces promoting and antagonizing separation. The major effector of centrosome separation is the kinesin Eg5. However, the identity and regulation of Eg5-antagonizing forces is less well characterized. By manipulating candidate components, we find that centrosome separation is reversible and that separated centrosomes congress toward a central position underneath the flat nucleus. This positioning mechanism requires microtubule polymerization, as well as actin polymerization. We identify perinuclear actin structures that form in late G2/early prophase and interact with microtubules emanating from the centrosomes. Disrupting these structures by breaking the interactions of the linker of nucleoskeleton and cytoskeleton (LINC) complex with perinuclear actin filaments abrogates this centrosome positioning mechanism and causes an increase in subsequent chromosome segregation errors. Our results demonstrate how geometrical cues from the cell nucleus coordinate the orientation of the emanating spindle poles before nuclear envelope breakdown.

Item Type: Article
Keywords: Eg5, FHOD1, G2/M transition, LINC complex, centrosome positioning, centrosome separation, centrosome tracking, mitotic entry, perinuclear actin, microtubules
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 07 Jul 2020 07:12
Last Modified: 07 Jul 2020 07:15
URI: http://sro.sussex.ac.uk/id/eprint/92378

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