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Molecular Biology Reports Nov 2022The process of cell division plays a vital role in cancer progression. Cell proliferation and error-free chromosomes segregation during mitosis are central events in... (Review)
Review
The process of cell division plays a vital role in cancer progression. Cell proliferation and error-free chromosomes segregation during mitosis are central events in life cycle. Mistakes during cell division generate changes in chromosome content and alter the balances of chromosomes number. Any defects in expression of TIF1 family proteins, SAC proteins network, mitotic checkpoint proteins involved in chromosome mis-segregation and cancer development. Here we discuss the function of organelles deal with the chromosome segregation machinery, proteins and correction mechanisms involved in the accurate chromosome segregation during mitosis.
Topics: Humans; Chromosome Segregation; Mitosis; Cell Cycle; M Phase Cell Cycle Checkpoints; Cell Cycle Proteins; Neoplasms; Kinetochores
PubMed: 35931874
DOI: 10.1007/s11033-022-07788-1 -
Transcription-replication conflicts at chromosomal fragile sites-consequences in M phase and beyond.Chromosoma Mar 2017Collision between the molecular machineries responsible for transcription and replication is an important source of genome instability. Certain transcribed regions known... (Review)
Review
Collision between the molecular machineries responsible for transcription and replication is an important source of genome instability. Certain transcribed regions known as chromosomal fragile sites are particularly prone to recombine and mutate in a manner that correlates with specific transcription and replication patterns. At the same time, these chromosomal fragile sites engage in aberrant DNA structures in mitosis. Here, we discuss the mechanistic details of transcription-replication conflicts including putative scenarios for R-loop-induced replication inhibition to understand how transcription-replication conflicts transition from S phase into various aberrant DNA structures in mitosis.
Topics: Animals; Cell Division; Chromosome Fragile Sites; DNA Replication; Humans; Mitosis; Transcription, Genetic
PubMed: 27796495
DOI: 10.1007/s00412-016-0617-2 -
Nature Cell Biology Apr 2008The anaphase-promoting complex (APC) mediates the ubiquitination and degradation of key M-phase regulators, including cyclins and the anaphase inhibitor securin....
The anaphase-promoting complex (APC) mediates the ubiquitination and degradation of key M-phase regulators, including cyclins and the anaphase inhibitor securin. Intriguingly, securin can also inhibit the degradation of cyclin B. This competition between substrates permits the accumulation of enough cyclin to drive entry into M phase.
Topics: Anaphase-Promoting Complex-Cyclosome; Animals; Cell Cycle Proteins; Cell Division; Mice; Nuclear Proteins; Proteins; Saccharomyces cerevisiae Proteins; Securin; Ubiquitin-Protein Ligase Complexes
PubMed: 18379598
DOI: 10.1038/ncb0408-381 -
Scientific Reports Nov 2017Mitochondrial activity in cells must be tightly controlled in response to changes in intracellular circumstances. Despite drastic changes in intracellular conditions and...
Mitochondrial activity in cells must be tightly controlled in response to changes in intracellular circumstances. Despite drastic changes in intracellular conditions and mitochondrial morphology, it is not clear how mitochondrial activity is controlled during M phase of the cell cycle. Here, we show that mitochondrial activity is drastically changed during M phase. Mitochondrial membrane potential changed during M phase progression. Mitochondria were polarized until metaphase to the same extent as mitochondria in interphase cells, but were depolarized at around telophase and cytokinesis. After cytokinesis, mitochondrial membrane potential was recovered. In addition, the generation of superoxide anions in mitochondria was significantly reduced at metaphase even in the presence of antimycin A, an inhibitor of complex III. These results suggest that the electron supply to the mitochondrial electron transfer chain is suppressed during M phase. This suppression might decrease the reactive oxygen species generated by the fragmentation of mitochondria during M phase.
Topics: Animals; Antimycin A; Cell Cycle; Cell Division; Cell Line; Membrane Potential, Mitochondrial; Mitochondria; Rats; Reactive Oxygen Species; Superoxides
PubMed: 29167496
DOI: 10.1038/s41598-017-15907-3 -
The Journal of Biological Chemistry Aug 2002Cl(-) channel activities vary during the cell cycle and are thought to play various roles including regulation of cell volume. We have shown previously that ClC-2...
Cl(-) channel activities vary during the cell cycle and are thought to play various roles including regulation of cell volume. We have shown previously that ClC-2 channels are directly phosphorylated and functionally regulated by the M phase-specific cyclin-dependent kinase p34(cdc2)/cyclin B. We investigate here to determine whether the expression levels of ClC-2 channel protein vary during the cell cycle. Immunoblot and immunocytochemical analyses of cells cycle-synchronized by serum depletion/replenishment reveal that ClC-2 channel protein is expressed predominantly at M phase in cells with two nuclei and a clear constriction ring, whereas RNA blot analysis shows that ClC-2 mRNA expression does not change during the cell cycle. Ubiquitin assays reveal that the ClC-2 channels are ubiquitinated at M phase, whereas the magnitude of ubiquitination is suppressed by incubation with olomoucine, an inhibitor of p34(cdc2)/cyclin B, and it is almost completely abolished in ClC-2 channels having an S632A mutation, which cannot be phosphorylated by p34(cdc2)/cyclin B, indicating that ubiquitination of ClC-2 channels requires phosphorylation by M phase-specific p34(cdc2)/cyclin B. Regulation at the post-transcriptional level, including phosphorylation-dependent ubiquitination, may contribute to M phase-specific expression of ClC-2 channels. Cell cycle-dependent regulation of expression at the protein level in addition to the regulation of function suggests that the ClC-2 channel plays a physiological role in the cell cycle.
Topics: Animals; CLC-2 Chloride Channels; Calcium Channels; Cell Cycle; Cell Division; Cell Line; Chloride Channels; Gene Expression Regulation; Heart; Humans; Mitosis; Myocardium; Phosphorylation; Rabbits; Rats; Recombinant Proteins; Transfection; Ubiquitin
PubMed: 12105212
DOI: 10.1074/jbc.M202105200 -
Cell Cycle (Georgetown, Tex.) 2014Centrosome size varies considerably during the cell cycle; it is greatest during metaphase, partly because of pericentriolar matrix recruitment and an increase in...
Centrosome size varies considerably during the cell cycle; it is greatest during metaphase, partly because of pericentriolar matrix recruitment and an increase in microtubule-organizing activity. However, the mechanism of centrosome maturation during M phase is poorly defined. In the present study, we identified and quantified centrosomal proteins during S and M phases using stable isotope labeling by amino acids in cell culture (SILAC) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified 991 proteins, of which 310 and 325 proteins were upregulated during S and M phases, respectively. Ubiquitinated proteins containing K48- and K63-linked polyubiquitin chains accumulated in the centrosomes during M phase, although 26S proteasome activity in the centrosomes did not markedly differ between S and M phases. Conversely, cytoplasmic dynein, which transports ubiquitinated proteins to the centrosomes, increased 2-fold in the centrosomes during M phase relative to S phase. Furthermore, PYR-41, a ubiquitin E1 inhibitor, reduced centrosome size during metaphase, causing increased aneuploidy. RNA interference suppression of Ecm29, which inhibits proteasome activity, decreased the accumulation of ubiquitinated proteins in the centrosomes. These results show that accumulation of ubiquitinated proteins promotes centrosome maturation during M phase and further suggest a novel function of centrosomes as a scaffold temporarily gathering intracellular ubiquitinated proteins.
Topics: Cell Division; Cell Line, Tumor; Centrosome; Humans; Polyubiquitin; S Phase; Ubiquitinated Proteins
PubMed: 24743317
DOI: 10.4161/cc.28896 -
Current Biology : CB Apr 2019Normal mitotic spindle assembly is a prerequisite for faithful chromosome segregation and unperturbed cell-cycle progression. Precise functioning of the spindle...
Normal mitotic spindle assembly is a prerequisite for faithful chromosome segregation and unperturbed cell-cycle progression. Precise functioning of the spindle machinery relies on conserved architectural features, such as focused poles, chromosome alignment at the metaphase plate, and proper spindle length. These morphological requirements can be achieved only within a compositionally distinct cytoplasm that results from cell-cycle-dependent regulation of specific protein levels and specific post-translational modifications. Here, we used cell-free extracts derived from Xenopus laevis eggs to recapitulate different phases of the cell cycle in vitro and to determine which components are required to render interphase cytoplasm spindle-assembly competent in the absence of protein translation. We found that addition of a nondegradable form of the master cell-cycle regulator cyclin B1 can indeed induce some biochemical and phenomenological characteristics of mitosis, but cyclin B1 alone is insufficient and actually deleterious at high levels for normal spindle assembly. In contrast, addition of a phosphomimetic form of the Greatwall-kinase effector Arpp19 with a specific concentration of nondegradable cyclin B1 rescued spindle bipolarity but resulted in larger-than-normal bipolar spindles with a misalignment of chromosomes. Both were corrected by the addition of exogenous Xkid (Xenopus homolog of human Kid/KIF22), indicating a role for this chromokinesin in regulating spindle length. These observations suggest that, of the many components degraded at mitotic exit and then replenished during the subsequent interphase, only a few are required to induce a cell-cycle transition that produces a spindle-assembly-competent cytoplasm.
Topics: Animals; Cell Nucleus Division; Chromosome Segregation; Ovum; Spindle Apparatus; Xenopus laevis
PubMed: 30930041
DOI: 10.1016/j.cub.2019.02.061 -
The International Journal of... Jun 1994Although a major concern in the development of multicellular organisms is cell differentiation, the construction of a multicellular system essentially depends on cell... (Review)
Review
Although a major concern in the development of multicellular organisms is cell differentiation, the construction of a multicellular system essentially depends on cell multiplication, which consists of genomic duplication and segregation. Recent progress has revealed that cyclin-dependent kinases (CDKs) are key components of a cell cycle engine that governs cell proliferation. This article focuses on how CDKs induce M-phase events characterized by nuclear membrane breakdown, chromosome condensation and mitotic spindle formation to assure genomic segregation.
Topics: Amino Acid Sequence; Animals; CDC2 Protein Kinase; Cell Cycle; Cell Division; Chromosomes; Cyclins; Female; Histones; Maturation-Promoting Factor; Mitosis; Molecular Sequence Data; Substrate Specificity
PubMed: 7981028
DOI: No ID Found -
Journal of Biological Rhythms Oct 2008In many phytoplankton species, cell division (mitosis) usually occurs at defined times of day. This timing is also observed under constant conditions, indicating that it...
In many phytoplankton species, cell division (mitosis) usually occurs at defined times of day. This timing is also observed under constant conditions, indicating that it is regulated by a circadian clock rather than by a simple response to the light-dark cycle. For those algae with cell cycles longer than a day, the clock opens a window of opportunity for mitosis at a particular time of day through which cells in an appropriate phase of the cell cycle can pass. Although the timing of mitosis is generally studied due to ease of measurement, for some phytoplankton the timing of S-phase is also circadian. This thus raises the possibility that mitosis is not directly gated by the clock but occurs instead at a defined interval (a constant G2 length) following a circadian controlled S-phase. To determine if the clock exercises independent control over the timing of both S- and M-phase, we measured the timing of both S- and M-phase in cultures of the dinoflagellate Lingulodinium grown under a variety of different photoperiods. We interpret the phase angles of both rhythms, in particular those resulting in a change in the length of G2, as an indication that the clock independently regulates the timing of S-phase and mitosis.
Topics: Animals; Cell Division; Cell Separation; Circadian Rhythm; Dinoflagellida; Eukaryota; Flow Cytometry; Light; Mitosis; Models, Biological; Photoperiod; Phytoplankton; S Phase; Time Factors
PubMed: 18838606
DOI: 10.1177/0748730408321749 -
The International Journal of... Jun 2013The role of polyamines at the G1/S boundary and in the G2/M phase of the cell cycle was studied using synchronized HeLa cells treated with thymidine or with thymidine...
The role of polyamines at the G1/S boundary and in the G2/M phase of the cell cycle was studied using synchronized HeLa cells treated with thymidine or with thymidine and aphidicolin. Synchronized cells were cultured in the absence or presence of α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, plus ethylglyoxal bis(guanylhydrazone) (EGBG), an inhibitor of S-adenosylmethionine decarboxylase. When polyamine content was reduced by treatment with DFMO and EGBG, the transition from G1 to S phase was delayed. In parallel, the level of p27(Kip1) was greatly increased, so its mechanism was studied in detail. Synthesis of p27(Kip1) was stimulated at the level of translation by a decrease in polyamine levels, because of the existence of long 5'-untranslated region (5'-UTR) in p27(Kip1) mRNA. Similarly, the transition from the G2/M to the G1 phase was delayed by a reduction in polyamine levels. In parallel, the number of multinucleate cells increased by 3-fold. This was parallel with the inhibition of cytokinesis due to an unusual distribution of actin and α-tubulin at the M phase. Since an association of polyamines with chromosomes was not observed by immunofluorescence microscopy at the M phase, polyamines may have only a minor role in structural changes of chromosomes at the M phase. In general, the involvement of polyamines at the G2/M phase was smaller than that at the G1/S boundary.
Topics: Adenosylmethionine Decarboxylase; Biogenic Polyamines; Cell Division; Cyclin-Dependent Kinase Inhibitor p27; Eflornithine; Enzyme Inhibitors; G1 Phase; G2 Phase; HeLa Cells; Humans; Mitoguazone; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; S Phase
PubMed: 23500523
DOI: 10.1016/j.biocel.2013.02.021