Dissociation of membrane–chromatin contacts is required for proper chromosome segregation in mitosis

The nuclear envelope (NE) aids in organizing the interphase genome by tethering chromatin to the nuclear periphery. During mitotic entry, NE–chromatin contacts are broken. Here, we report on the consequences of impaired NE removal from chromatin for cell division of human cells. Using a membrane–chromatin tether that cannot be dissociated when cells enter mitosis, we show that a failure in breaking membrane–chromatin interactions impairs mitotic chromatin organization, chromosome segregation and cytokinesis, and induces an aberrant NE morphology in postmitotic cells. In contrast, chromosome segregation and cell division proceed successfully when membrane attachment to chromatin is induced during metaphase, after chromosomes have been singularized and aligned at the metaphase plate. These results indicate that the separation of membranes and chromatin is critical during prometaphase to allow for proper chromosome compaction and segregation. We propose that one cause of these defects is the multivalency of membrane–chromatin interactions.

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Chromosome–nuclear envelope tethering – a process that orchestrates homologue pairing during plant meiosis?

Journal of Cell Science ◽

10.1242/jcs.243667 ◽

2020 ◽

Vol 133 (15) ◽

pp. jcs243667

Author(s):

Adél Sepsi ◽

Trude Schwarzacher

Keyword(s):

Nuclear Envelope ◽

Chromosome Segregation ◽

Higher Plants ◽

Nuclear Periphery ◽

Genetic Material ◽

Strand Break ◽

Genome Integrity ◽

Homologous Chromosomes ◽

Prophase I ◽

Plant Meiosis

ABSTRACTDuring prophase I of meiosis, homologous chromosomes pair, synapse and exchange their genetic material through reciprocal homologous recombination, a phenomenon essential for faithful chromosome segregation. Partial sequence identity between non-homologous and heterologous chromosomes can also lead to recombination (ectopic recombination), a highly deleterious process that rapidly compromises genome integrity. To avoid ectopic exchange, homology recognition must be extended from the narrow position of a crossover-competent double-strand break to the entire chromosome. Here, we review advances on chromosome behaviour during meiotic prophase I in higher plants, by integrating centromere- and telomere dynamics driven by cytoskeletal motor proteins, into the processes of homologue pairing, synapsis and recombination. Centromere–centromere associations and the gathering of telomeres at the onset of meiosis at opposite nuclear poles create a spatially organised and restricted nuclear state in which homologous DNA interactions are favoured but ectopic interactions also occur. The release and dispersion of centromeres from the nuclear periphery increases the motility of chromosome arms, allowing meiosis-specific movements that disrupt ectopic interactions. Subsequent expansion of interstitial synapsis from numerous homologous interactions further corrects ectopic interactions. Movement and organisation of chromosomes, thus, evolved to facilitate the pairing process, and can be modulated by distinct stages of chromatin associations at the nuclear envelope and their collective release.

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Yeast silencing factor Sir4 and a subset of nucleoporins form a complex distinct from nuclear pore complexes

The Journal of Cell Biology ◽

10.1083/jcb.201609049 ◽

2017 ◽

Vol 216 (10) ◽

pp. 3145-3159 ◽

Cited By ~ 13

Author(s):

Diego L. Lapetina ◽

Christopher Ptak ◽

Ulyss K. Roesner ◽

Richard W. Wozniak

Keyword(s):

Nuclear Envelope ◽

Nuclear Pore Complex ◽

E3 Ligase ◽

Chromatin Organization ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Chromatin Interactions ◽

Sumo E3 Ligase ◽

Pore Complexes

Interactions occurring at the nuclear envelope (NE)–chromatin interface influence both NE structure and chromatin organization. Insights into the functions of NE–chromatin interactions have come from the study of yeast subtelomeric chromatin and its association with the NE, including the identification of various proteins necessary for tethering subtelomeric chromatin to the NE and the silencing of resident genes. Here we show that four of these proteins—the silencing factor Sir4, NE-associated Esc1, the SUMO E3 ligase Siz2, and the nuclear pore complex (NPC) protein Nup170—physically and functionally interact with one another and a subset of NPC components (nucleoporins or Nups). Importantly, this group of Nups is largely restricted to members of the inner and outer NPC rings, but it lacks numerous others including cytoplasmically and nucleoplasmically positioned Nups. We propose that this Sir4-associated Nup complex is distinct from holo-NPCs and that it plays a role in subtelomeric chromatin organization and NE tethering.

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Aurora kinases orchestrate mitosis; who are the players?

BioMolecular Concepts ◽

10.1515/bmc.2010.014 ◽

2010 ◽

Vol 1 (2) ◽

pp. 147-155 ◽

Cited By ~ 1

Author(s):

Annie Molla

Keyword(s):

Cell Division ◽

Chromosome Segregation ◽

Metaphase Plate ◽

Spindle Assembly ◽

Aurora Kinases ◽

Threonine Kinases

AbstractThe Aurora are a conserved family of serine/threonine kinases with essential functions in cell division. In mitosis, Aurora kinases are required for chromosome segregation, condensation and orientation in the metaphase plate, spindle assembly, and the completion of cytokinesis. This review presents the Aurora kinases, their partners and how their interactions impact on the different mitotic functions.

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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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Cell Division in Oedogonium II. Nuclear Division in O. Cardiacum

Australian Journal of Biological Sciences ◽

10.1071/bi9700071 ◽

1970 ◽

Vol 23 (1) ◽

pp. 71 ◽

Cited By ~ 47

Author(s):

JD Pickett-Heaps ◽

LC Fowke

Keyword(s):

Cell Division ◽

Granular Material ◽

Nuclear Envelope ◽

Nuclear Division ◽

Complex Structure ◽

Metaphase Plate ◽

Spindle Axis ◽

Large Numbers

Nuclear division in O. cardiacum is described. Before division, the nucleus enlarges considerably. At prophase, the nucleolus starts dispersing and kinetochores appear on the condensing chromatin, situated and oriented apparently at random in the nucleus. By prometaphase, the kinetochore pairs become aligned along the spindle axis before moving into the metaphase-plate configuration; this supports an earlier theory explaining metakinesis. During prophase and metaphase particularly, the nuclear envelope at the poles forms channels that extend for some distance into the cytoplasm; these may also bifurcate. The nucleolus disperses but remains in the intranuclear spindle throughout division as a loosely knit skein of granular material. The kinetochores have a complex structure, up to seven distinct layers being detectable; the kinetochore pairs split, and then migrate polewards at anaphase with the rest of the chromosome trailing behind. Large numbers of microtubules run from the kinetochore into evaginations of the nuclear envelope which increase in size during anaphase. The spindle grows in length considerably during anaphase, this coinciding with a proliferation of interzonal microtubules, first seen amongst the trailing chromosome arms. The nuclear envelope enclosing the spindle becomes severely stretched at this stage; it contracts closely around each of the daughter nuclei, isolating them from the rest of the spindle (including microtubules and the remains of the nucleolus). The spindle then collapses; the nuclei come together and then flatten against one another; between them, vesicles and other components of the septum collect amongst a large number of transversely oriented micro tubules.

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DUSP7 Regulates the Activity of ERK2 to Promote Proper Chromosome Alignment During Cell Division

10.1101/2020.06.05.137364 ◽

2020 ◽

Author(s):

Xiao Guo ◽

Yenni A. Garcia ◽

Ivan Ramirez ◽

Erick F. Velasquez ◽

Lucy W. Gao ◽

...

Keyword(s):

Cell Division ◽

Chromosome Segregation ◽

Human Cell ◽

Mitotic Chromosome ◽

Marked Decrease ◽

Metaphase Plate ◽

Chromosome Congression ◽

Dual Specificity ◽

Chromosome Alignment ◽

Chemical Inhibition

SUMMARYHuman cell division is a highly regulated process that relies on the accurate capture and movement of chromosomes to the metaphase plate. Errors in the fidelity of chromosome congression and alignment can lead to improper chromosome segregation, which is correlated with aneuploidy and tumorigenesis. Here we show that the dual specificity phosphatase DUSP7 is important for regulating chromosome alignment. DUSP7 bound to ERK2 and regulated the abundance of active phospho-ERK2 through its phosphatase activity. Overexpression of DUSP7, but not catalytic dead mutants, led to a marked decrease in phopho-ERK2 and mitotic chromosome misalignment, while knockdown of DUSP7 also led to defective chromosome congression that resulted in a prolonged mitosis. Consistently, chemical inhibition of the MEK kinase that phosphorylates ERK2 or ERK2 itself led to chromosome alignment defects. Our results support a model where MEK phosphorylation and DUSP7 dephosphorylation regulate the levels of active phospho-ERK2 to promote proper cell division.

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The Ultrastructure of the Nuclear Events of Binary Fission in Paramecium bursaria and the Effects of Colchicine on Cell Division

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051396 ◽

1974 ◽

Vol 32 ◽

pp. 276-277

Author(s):

L. M. Lewis

Keyword(s):

Cell Division ◽

Nuclear Envelope ◽

Condensed Chromatin ◽

Binary Fission ◽

Paramecium Bursaria ◽

Nuclear Events ◽

Division Axis

The effects of colchicine on extranuclear microtubules associated with the macronucleus of Paramecium bursaria were studied to determine the possible role that these microtubules play in controlling the shape of the macronucleus. In the course of this study, the ultrastructure of the nuclear events of binary fission in control cells was also studied.During interphase in control cells, the micronucleus contains randomly distributed clumps of condensed chromatin and microtubular fragments. Throughout mitosis the nuclear envelope remains intact. During micronuclear prophase, cup-shaped microfilamentous structures appear that are filled with condensing chromatin. Microtubules are also present and are parallel to the division axis.

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Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B

Nucleic Acids Research ◽

10.1093/nar/gkaa449 ◽

2020 ◽

Vol 48 (12) ◽

pp. 6583-6596

Author(s):

Akiko Fujimura ◽

Yuki Hayashi ◽

Kazashi Kato ◽

Yuichiro Kogure ◽

Mutsuro Kameyama ◽

...

Keyword(s):

Chromosome Segregation ◽

Protein Complex ◽

Metaphase Plate ◽

Nucleolar Protein ◽

Aurora B ◽

Mitotic Progression ◽

Mitotic Chromosomes ◽

Nucleolar Proteins ◽

Chromatid Cohesion ◽

Wd Repeat

Abstract The nucleolus is a membrane-less nuclear structure that disassembles when cells undergo mitosis. During mitosis, nucleolar factors are thus released from the nucleolus and dynamically change their subcellular localization; however, their functions remain largely uncharacterised. Here, we found that a nucleolar factor called nucleolar protein 11 (NOL11) forms a protein complex with two tryptophan-aspartic acid (WD) repeat proteins named WD-repeat protein 43 (WDR43) and Cirhin in mitotic cells. This complex, referred to here as the NWC (NOL11-WDR43-Cirhin) complex, exists in nucleoli during interphase and translocates to the periphery of mitotic chromosomes, i.e., perichromosomal regions. During mitotic progression, both the congression of chromosomes to the metaphase plate and sister chromatid cohesion are impaired in the absence of the NWC complex, as it is required for the centromeric enrichment of Aurora B and the associating phosphorylation of histone H3 at threonine 3. These results reveal the characteristics of a novel protein complex consisting of nucleolar proteins, which is required for regulating kinetochores and centromeres to ensure faithful chromosome segregation.

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Genes Required for Aerial Growth, Cell Division, and Chromosome Segregation Are Targets of WhiA before Sporulation in Streptomyces venezuelae

mBio ◽

10.1128/mbio.00684-13 ◽

2013 ◽

Vol 4 (5) ◽

Cited By ~ 61

Author(s):

Matthew J. Bush ◽

Maureen J. Bibb ◽

Govind Chandra ◽

Kim C. Findlay ◽

Mark J. Buttner

Keyword(s):

Cell Division ◽

Chromosome Segregation ◽

Regulatory Networks ◽

Liquid Culture ◽

Biological Processes ◽

Streptomyces Venezuelae ◽

Content Type ◽

Master Regulators ◽

Aerial Growth ◽

Genes Encoding

ABSTRACTWhiA is a highly unusual transcriptional regulator related to a family of eukaryotic homing endonucleases. WhiA is required for sporulation in the filamentous bacteriumStreptomyces, but WhiA homologues of unknown function are also found throughout the Gram-positive bacteria. To better understand the role of WhiA inStreptomycesdevelopment and its function as a transcription factor, we identified the WhiA regulon through a combination of chromatin immunoprecipitation-sequencing (ChIP-seq) and microarray transcriptional profiling, exploiting a new model organism for the genus,Streptomyces venezuelae, which sporulates in liquid culture. The regulon encompasses ~240 transcription units, and WhiA appears to function almost equally as an activator and as a repressor. Bioinformatic analysis of the upstream regions of the complete regulon, combined with DNase I footprinting, identified a short but highly conserved asymmetric sequence, GACAC, associated with the majority of WhiA targets. Construction of a null mutant showed thatwhiAis required for the initiation of sporulation septation and chromosome segregation inS. venezuelae, and several genes encoding key proteins of theStreptomycescell division machinery, such asftsZ,ftsW, andftsK, were found to be directly activated by WhiA during development. Several other genes encoding proteins with important roles in development were also identified as WhiA targets, including the sporulation-specific sigma factor σWhiGand the diguanylate cyclase CdgB. Cell division is tightly coordinated with the orderly arrest of apical growth in the sporogenic cell, andfilP, encoding a key component of the polarisome that directs apical growth, is a direct target for WhiA-mediated repression during sporulation.IMPORTANCESince the initial identification of the genetic loci required forStreptomycesdevelopment, all of thebldandwhidevelopmental master regulators have been cloned and characterized, and significant progress has been made toward understanding the cell biological processes that drive morphogenesis. A major challenge now is to connect the cell biological processes and the developmental master regulators by dissecting the regulatory networks that link the two. Studies of these regulatory networks have been greatly facilitated by the recent introduction ofStreptomyces venezuelaeas a new model system for the genus, a species that sporulates in liquid culture. Taking advantage ofS. venezuelae, we have characterized the regulon of genes directly under the control of one of these master regulators, WhiA. Our results implicate WhiA in the direct regulation of key steps in sporulation, including the cessation of aerial growth, the initiation of cell division, and chromosome segregation.

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