Breaking down the wall: the nuclear envelope during mitosis

Abstract

A defining feature of eukaryotic cells is the nucleus, which houses the genome inside the nuclear envelope (NE): a double lipid bilayer that separates the nuclear and cytoplasmic materials. Although the NE is commonly viewed as a barrier that is overcome only by embedded nuclear pore complexes (NPCs) that facilitate nuclear-cytoplasmic trafficking, recent work in a wide range of eukaryotes reveals that the NE is a dynamic organelle that is modified each time the cell divides to ultimately establish two functional daughter nuclei. Here, we review how studies of divergent mitotic strategies have helped elucidate common properties of NE biology that allow it to function throughout the cell cycle.

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

“…Controlled NE disassembly at the onset of nuclear division is a conserved process whose extent varies along a continuum across eukaryotes (Guttinger et al, 2009; Smoyer and Jaspersen, 2014), with mitosis being classified as open , semi-open and closed (Makarova and Oliferenko, 2016; Sazer et al, 2014). In most metazoans including vertebrates, complete NEBD occurs at the prophase-prometaphase stage and involves the disassembly of nuclear pore complexes (NPCs), lamins, and outer and inner nuclear membranes, whose components are redistributed throughout the endoplasmic reticulum and cytoplasm.…”

Bursting the Bubble – Nuclear Envelope Rupture as a Path to Genomic Instability?

“…Nuclear envelope breakdown has been studied in extensive detail during mitosis, where the nuclear lamina disassembles in late prophase (prometaphase) in a highly regulated process [13]. In mitosis, disassembly of the NE is mediated by phosphorylation of nuclear pore proteins, lamins, and other NE proteins by protein kinase C (PKC) and cyclin dependent kinase 1 (Cdk1) [14, 15].…”

Nuclear envelope rupture drives genome instability in cancer

“…In physiologically normal cells, breakdown of the nuclear envelope occurs only during mitosis to enable condensed chromosomes to freely segregate to daughter cells (Smoyer and Jaspersen, 2014). This highly regulated process of mitotic nuclear envelope disassembly is governed in large part by activation of the mitotic kinase Cdk1, which phosphorylates key components of the lamina and nuclear pore complexes to promote their disassembly (Heald and McKeon, 1990; Peter et al.…”

“…Alterations in the microtubule cytoskeleton and/or increases in centrosome number may also play a role in promoting nuclear envelope rupture. During mitosis, centrosomes and microtubules play important roles in facilitating nuclear envelope breakdown, and depletion of centrosomes has been shown to delay nuclear envelope disassembly (Smoyer and Jaspersen, 2014). Thus it is plausible that extra centrosomes, which are a hallmark of cancer cells, facilitate nuclear envelope rupture.…”