Mitotic Nuclear Envelope Breakdown and Spindle Nucleation Are Controlled by Interphase Contacts between Centromeres and the Nuclear Envelope

Publication date: Available online 23 November 2016
Source:Developmental Cell
Author(s): Alfonso Fernández-Álvarez, Cécile Bez, Eileen T. O'Toole, Mary Morphew, Julia Promisel Cooper
Faithful genome propagation requires coordination between nuclear envelope (NE) breakdown, spindle formation, and chromosomal events. The conserved linker of nucleoskeleton and cytoskeleton (LINC) complex connects fission yeast centromeres and the centrosome, across the NE, during interphase. During meiosis, LINC connects the centrosome with telomeres rather than centromeres. We previously showed that loss of telomere-LINC contacts compromises meiotic spindle formation. Here, we define the precise events regulated by telomere-LINC contacts and address the analogous possibility that centromeres regulate mitotic spindle formation. We develop conditionally inactivated LINC complexes in which the conserved SUN-domain protein Sad1 remains stable but severs interphase centromere-LINC contacts. Strikingly, the loss of such contacts abolishes spindle formation. We pinpoint the defect to a failure in the partial NE breakdown required for centrosome insertion into the NE, a step analogous to mammalian NE breakdown. Thus, interphase chromosome-LINC contacts constitute a cell-cycle control device linking nucleoplasmic and cytoplasmic events.

Graphical abstract

Teaser

The role of interphase centromere-LINC contacts has been a longstanding intractable mystery. Fernández-Álvarez et al. generate a mutation that severs these centromere-LINC contacts, leading to failed nuclear envelope breakdown and, in turn, failed spindle assembly. Thus, centromere-LINC contacts couple chromosomal events with cytoplasmic events that propel the cell cycle.


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