Abstract
The segregation of the chromosomes during mitosis is an important process, in which the replicated DNA content is properly allocated into two daughter cells. To ensure their genomic integrity, cells present an essential surveillance mechanism known as the spindle assembly checkpoint (SAC), which monitors the bipolar attachment of the mitotic spindle to chromosomes to prevent errors that would result in chromosome mis-segregation and aneuploidy. Multiple components of the nuclear pore complex (NPC), a gigantic protein complex that forms a channel through the nuclear envelope to allow nucleocytoplasmic exchange of macromolecules, were shown to be critical for faithful cell division and implicated in the regulation of different steps of the mitotic process, including kinetochore and spindle assembly as well as the SAC. In this review, we will describe current knowledge about the interconnection between the NPC and the SAC in an evolutional perspective, which primarily relies on the two mitotic checkpoint regulators, Mad1 and Mad2. We will further discuss the role of NPC constituents, the nucleoporins, in kinetochore and spindle assembly and the formation of the mitotic checkpoint complex during mitosis and interphase.
Highlights
Nuclear pore complexes (NPCs) are large protein complexes that are embedded in the nuclear envelope (NE), thereby spanning the inner nuclear membrane (INM) and the outer nuclear membrane (ONM) [1]
This study revealed that Nup358 is important for the sumoylation and the subsequent recruitment of DNA topoisomerase IIα (TopoIIα) to centromeres
Beyond the role in the nucleocytoplasmic transport during interphase, some nucleoporins are of outmost importance at distinct steps of mitosis: for example, the Nup107-160 complex and Nup358 for proper spindle assembly, Tpr and Nup153 for the spindle assembly checkpoint, or Nup98 and its partner Rae1 for the anaphase-promoting complex/cyclosome (APC/C)
Summary
Nuclear pore complexes (NPCs) are large protein complexes that are embedded in the nuclear envelope (NE), thereby spanning the inner nuclear membrane (INM) and the outer nuclear membrane (ONM) [1]. 5 × 107 NPCs/nucleus in mature Xenopus oocyte nuclei [6], and about 200 NPCs/nucleus in yeast [4] Despite these differences in molecular weight and number, NPCs from distinct species share a roughly tripartite structural organization with an eightfold rotational symmetry [7,8,9,10,11,12,13]. They are composed of a central scaffold ( called central framework or spoke complex), which is continuous with the cytoplasmic and the nucleoplasmic ring moieties and which is enclosing a central pore. We will discuss common characteristics and highlight species-specific differences in the interplay between these two cellular complexes
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