Faculty Opinions recommendation of Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry.

ABSTRACTThe G2-M transition inAspergillus nidulansrequires the NIMA kinase, the founding member of the Nek kinase family. Inactivation of NIMA results in a late G2arrest, while overexpression of NIMA is sufficient to promote mitotic events independently of cell cycle phase. Endogenously tagged NIMA-GFP has dynamic mitotic localizations appearing first at the spindle pole body and then at nuclear pore complexes before transitioning to within nuclei and the mitotic spindle and back at the spindle pole bodies at mitotic exit, suggesting that it functions sequentially at these locations. Since NIMA is indispensable for mitotic entry, it has been difficult to determine the requirement of NIMA for subaspects of mitosis. We show here that when NIMA is partially inactivated, although mitosis can be initiated, a proportion of cells fail to successfully generate two daughter nuclei. We further define the mitotic defects to show that normal NIMA function is required for the formation of a bipolar spindle, nuclear pore complex disassembly, completion of chromatin segregation, and the normal structural rearrangements of the nuclear envelope required to generate two nuclei from one. In the remaining population of cells that enter mitosis with inadequate NIMA, two daughter nuclei are generated in a manner dependent on the spindle assembly checkpoint, indicating highly penetrant defects in mitotic progression without sufficient NIMA activity. This study shows that NIMA is required not only for mitotic entry but also sequentially for successful completion of stage-specific mitotic events.

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SUMO-Based Regulation of Nuclear Positioning to Spatially Regulate Homologous Recombination Activities at Replication Stress Sites

Genes ◽

10.3390/genes12122010 ◽

2021 ◽

Vol 12 (12) ◽

pp. 2010

Author(s):

Kamila Schirmeisen ◽

Sarah A. E. Lambert ◽

Karol Kramarz

Keyword(s):

Homologous Recombination ◽

Replication Fork ◽

Replication Stress ◽

Dna Lesions ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Replication Forks ◽

Nuclear Positioning ◽

Nuclear Compartment ◽

Pore Complexes

DNA lesions have properties that allow them to escape their nuclear compartment to achieve DNA repair in another one. Recent studies uncovered that the replication fork, when its progression is impaired, exhibits increased mobility when changing nuclear positioning and anchors to nuclear pore complexes, where specific types of homologous recombination pathways take place. In yeast models, increasing evidence points out that nuclear positioning is regulated by small ubiquitin-like modifier (SUMO) metabolism, which is pivotal to maintaining genome integrity at sites of replication stress. Here, we review how SUMO-based pathways are instrumental to spatially segregate the subsequent steps of homologous recombination during replication fork restart. In particular, we discussed how routing towards nuclear pore complex anchorage allows distinct homologous recombination pathways to take place at halted replication forks.

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Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry

Molecular Biology of the Cell ◽

10.1091/mbc.e12-07-0558 ◽

2012 ◽

Vol 23 (24) ◽

pp. 4713-4724 ◽

Cited By ~ 13

Author(s):

Jeanne N. Jodoin ◽

Mohammad Shboul ◽

Poojitha Sitaram ◽

Hala Zein-Sabatto ◽

Bruno Reversade ◽

...

Keyword(s):

Male Meiosis ◽

Human Cells ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Nuclear Surface ◽

Mitotic Entry ◽

Male Germline ◽

Germline Expression ◽

Cultured Human Cells ◽

Pore Complexes

Recruitment of dynein motors to the nuclear surface is an essential step for nucleus–centrosome coupling in prophase. In cultured human cells, this dynein pool is anchored to nuclear pore complexes through RanBP2–Bicaudal D2 (BICD2) and Nup133– centromere protein F (CENP-F) networks. We previously reported that the asunder (asun) gene is required in Drosophila spermatocytes for perinuclear dynein localization and nucleus–centrosome coupling at G2/M of male meiosis. We show here that male germline expression of mammalian Asunder (ASUN) protein rescues asun flies, demonstrating evolutionary conservation of function. In cultured human cells, we find that ASUN down-regulation causes reduction of perinuclear dynein in prophase of mitosis. Additional defects after loss of ASUN include nucleus–centrosome uncoupling, abnormal spindles, and multinucleation. Coimmunoprecipitation and overlapping localization patterns of ASUN and lissencephaly 1 (LIS1), a dynein adaptor, suggest that ASUN interacts with dynein in the cytoplasm via LIS1. Our data indicate that ASUN controls dynein localization via a mechanism distinct from that of either BICD2 or CENP-F. We present a model in which ASUN promotes perinuclear enrichment of dynein at G2/M that facilitates BICD2- and CENP-F-mediated anchoring of dynein to nuclear pore complexes.

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CDK1 and PLK1 co-ordinate the disassembly and re-assembly of the Nuclear Envelope in vertebrate mitosis

10.1101/185660 ◽

2017 ◽

Author(s):

Ines J de Castro ◽

Raquel Sales Gil ◽

Lorena Ligammari ◽

Maria Laura Di Giacinto ◽

Paola Vagnarelli

Keyword(s):

Dna Repair ◽

Cell Division ◽

Nuclear Envelope ◽

Genetic Instability ◽

Nuclear Pore ◽

Lamin A ◽

Nuclear Pore Complexes ◽

Regulatory Pathways ◽

Mitotic Entry ◽

Pore Complexes

ABSTRACTMicronuclei (MN) arise from chromosomes or fragments that fail to be incorporated into the primary nucleus after cell division. These structures are a major source of genetic instability caused by DNA repair and replication defects coupled to aberrant Nuclear Envelope (NE). These problems ultimately lead to a spectrum of chromosome rearrangements called chromothripsis, a phenomenon that is a hallmark of several cancers. Despite its importance, the molecular mechanism at the origin of this instability is still not understood. Here we show that lagging chromatin, although it can efficiently assemble Lamin A/C, always fails to recruit Nuclear Pore Complexes (NPCs) proteins and that Polo-Like Kinase (PLK1) negatively regulates the NPC assembly. We also provide evidence for the requirement of PLK1 activity for the disassembly of NPCs, but not Lamina (A/C), at mitotic entry. Altogether this study reveals the existence of independent regulatory pathways for Lamin A/C and NPC reorganization during mitosis where Lamin A targeting to the chromatin is controlled by CDK1 activity (a clock-based model) while the NPC loading is also spatially monitored by PLK1.

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Nuclear Envelope Dynamics During Mitosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100103188 ◽

1988 ◽

Vol 46 ◽

pp. 224-225

Author(s):

Brian Burke

Keyword(s):

Nuclear Envelope ◽

Membrane Vesicles ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Animal Cells ◽

Interphase Chromosome ◽

Lamin B ◽

Chromosome Architecture ◽

Complex Membrane ◽

Pore Complexes

The nuclear envelope is a complex membrane structure that forms the boundary of the nuclear compartment in eukaryotes. It regulates the passage of macromolecules between the two compartments and may be important for organizing interphase chromosome architecture. In interphase animal cells it forms a remarkably stable structure consisting of a double membrane ouerlying a protein meshwork or lamina and penetrated by nuclear pore complexes. The latter form the channels for nucleocytoplasmic exchange of macromolecules, At the onset of mitosis, however, it rapidly disassembles, the membranes fragment to yield small vesicles and the lamina, which is composed of predominantly three polypeptides, lamins R, B and C (MW approx. 74, 68 and 65 kDa respectiuely), breaks down. Lamins B and C are dispersed as monomers throughout the mitotic cytoplasm, while lamin B remains associated with the nuclear membrane vesicles.

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