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Nature Reviews. Molecular Cell Biology Jan 2013In eukaryotes, chromosome segregation during cell division is facilitated by the kinetochore, a multiprotein structure that is assembled on centromeric DNA. The... (Review)
Review
In eukaryotes, chromosome segregation during cell division is facilitated by the kinetochore, a multiprotein structure that is assembled on centromeric DNA. The kinetochore attaches chromosomes to spindle microtubules, modulates the stability of these attachments and relays the microtubule-binding status to the spindle assembly checkpoint (SAC), a cell cycle surveillance pathway that delays chromosome segregation in response to unattached kinetochores. Recent studies are shaping current thinking on how each of these kinetochore-centred processes is achieved, and how their integration ensures faithful chromosome segregation, focusing on the essential roles of kinase-phosphatase signalling and the microtubule-binding KMN protein network.
Topics: Cell Division; Chromosome Segregation; Cytoskeletal Proteins; Humans; Kinetochores; M Phase Cell Cycle Checkpoints; Microtubule-Associated Proteins; Microtubules; Mitosis; Nuclear Proteins; Signal Transduction; Spindle Apparatus
PubMed: 23258294
DOI: 10.1038/nrm3494 -
Methods in Molecular Biology (Clifton,... 2022The cell division cycle is a fundamental process required for proliferation of all living organisms. The eukaryotic cell cycle follows a basic template with an ordered...
The cell division cycle is a fundamental process required for proliferation of all living organisms. The eukaryotic cell cycle follows a basic template with an ordered series of events beginning with G1 (Gap1) phase, followed successively by S (Synthesis) phase, G2 (Gap 2) phase, and M-phase (Mitosis). The process is tightly regulated in response to signals from both the internal and external milieu. The budding yeast S. cerevisiae is an outstanding model for the study of the cell cycle and its regulatory process. The basic events and regulatory processes of the S. cerevisiae cell cycle are highly conserved with other eukaryotes. The organism grows rapidly in simple medium, has a sequenced annotated genome, well-established genetics, and is amenable to analysis by proteomics and microscopy. Additionally, a range of tools and techniques are available to generate cultures of S. cerevisiae that are homogenously arrested or captured at specific phases of the cell cycle and upon release from that arrest these can be used to monitor cell cycle events as the cells synchronously proceed through a division cycle. In this chapter, we describe a series of commonly used techniques that are used to generate synchronized populations of S. cerevisiae and provide an overview of methods that can be used to monitor the progression of the cells through the cell division cycle.
Topics: Cell Count; Cell Cycle; Mitosis; Saccharomyces cerevisiae
PubMed: 36045205
DOI: 10.1007/978-1-0716-2736-5_12 -
Toxicology and Applied Pharmacology Aug 2011Natural flavonoids have diverse pharmacological activities, including anti-oxidative, anti-inflammatory, and anti-cancer activities. In this study, we investigated the... (Comparative Study)
Comparative Study
Natural flavonoids have diverse pharmacological activities, including anti-oxidative, anti-inflammatory, and anti-cancer activities. In this study, we investigated the molecular mechanism underlying the action of 5-methoxyflavanone (5-MF) which has a strong bioavailability and metabolic stability. Our results show that 5-MF inhibited the growth and clonogenicity of HCT116 human colon cancer cells, and that it activated DNA damage responses, as revealed by the accumulation of p53 and the phosphorylation of DNA damage-sensitive proteins, including ataxia-telangiectasia mutated (ATM) at Ser1981, checkpoint kinase 2 (Chk2) at Thr68, and histone H2AX at Ser139. 5-MF-induced DNA damage was confirmed in a comet tail assay. We also found that 5-MF increased the cleavage of caspase-2 and -7, leading to the induction of apoptosis. Pretreatment with the ATM inhibitor KU55933 enhanced 5-MF-induced γ-H2AX formation and caspase-7 cleavage. HCT116 cells lacking p53 (p53(-/-)) or p21 (p21(-/-)) exhibited increased sensitivity to 5-MF compared to wild-type cells. 5-MF further induced autophagy via an ERK signaling pathway. Blockage of autophagy with the MEK inhibitor U0126 potentiated 5-MF-induced γ-H2AX formation and caspase-2 activation. These results suggest that a caspase-2 cascade mediates 5-MF-induced anti-tumor activity, while an ATM/Chk2/p53/p21 checkpoint pathway and ERK-mediated autophagy act as a survival program to block caspase-2-mediated apoptosis induced by 5-MF.
Topics: Apoptosis; Autophagy; Cell Cycle; Cell Division; Cell Survival; Flavones; G2 Phase; HCT116 Cells; Humans
PubMed: 21616090
DOI: 10.1016/j.taap.2011.05.003 -
Molecular Biology of the Cell Jan 2001Caldesmon is phosphorylated by cdc2 kinase during mitosis, resulting in the dissociation of caldesmon from microfilaments. To understand the physiological significance...
Caldesmon is phosphorylated by cdc2 kinase during mitosis, resulting in the dissociation of caldesmon from microfilaments. To understand the physiological significance of phosphorylation, we generated a caldesmon mutant replacing all seven cdc2 phosphorylation sites with Ala, and examined effects of expression of the caldesmon mutant on M-phase progression. We found that microinjection of mutant caldesmon effectively blocked early cell division of Xenopus embryos. Similar, though less effective, inhibition of cytokinesis was observed with Chinese hamster ovary (CHO) cells microinjected with 7th mutant. When mutant caldesmon was introduced into CHO cells either by protein microinjection or by inducible expression, delay of M-phase entry was observed. Finally, we found that 7th mutant inhibited the disassembly of microfilaments during mitosis. Wild-type caldesmon, on the other hand, was much less potent in producing these three effects. Because mutant caldesmon did not inhibit cyclin B/cdc2 kinase activity, our results suggest that alterations in microfilament assembly caused by caldesmon phosphorylation are important for M-phase progression.
Topics: Actin Cytoskeleton; Animals; Binding Sites; CDC2 Protein Kinase; CHO Cells; Calmodulin-Binding Proteins; Cell Division; Cricetinae; Embryo, Mammalian; Embryo, Nonmammalian; Microinjections; Microscopy, Fluorescence; Mitosis; Mutation; Phosphorylation; Rats; Transfection; Xenopus
PubMed: 11160835
DOI: 10.1091/mbc.12.1.239 -
Trends in Microbiology Jun 1996It is usually assumed that most prokaryotes, when given appropriate nutrients, can grow and divide in the absence of other cells of the same species. However, recent... (Review)
Review
It is usually assumed that most prokaryotes, when given appropriate nutrients, can grow and divide in the absence of other cells of the same species. However, recent studies have suggested that, for growth, prokaryotes need to communicate with each other using signalling molecules, and a variety of 'eukaryotic' hormones have been shown to stimulate bacterial growth. These observations have important implications for our understanding of bacterial pathogenicity.
Topics: Animals; Bacteria; Bacterial Physiological Phenomena; Cell Division; Hormones; Pheromones; Signal Transduction; Virulence
PubMed: 8795160
DOI: 10.1016/0966-842X(96)10035-4 -
Molecular Biology of the Cell Mar 2018
Topics: Animals; Cell Division; Congresses as Topic; Cytokinesis; Humans
PubMed: 29535170
DOI: 10.1091/mbc.E17-11-0671 -
Cell Structure and Function Jul 1984
Review
Topics: Anaphase; Animals; Cell Cycle; Cell Division; Cell Survival; Meiosis; Mitosis; Spindle Apparatus
PubMed: 6383636
DOI: 10.1247/csf.9.supplement_s73 -
Biology of the Cell Nov 1998This article reviews cell cycle changes that occur during midblastula transition (MBT) in Xenopus laevis based on research carried out in the authors' laboratory.... (Review)
Review
This article reviews cell cycle changes that occur during midblastula transition (MBT) in Xenopus laevis based on research carried out in the authors' laboratory. Blastomeres dissociated from the animal cap of blastulae, as well as those in an intact embryo, divide synchronously with a constant cell cycle duration in vitro, up to the 12th cell cycle regardless of their cell sizes. During this synchronous cleavage, cell sizes of blastomeres become variable because of repeated unequal cleavage. After the 12th cell cycle blastomeres require contact with an appropriate protein substrate to continue cell division. When nucleocytoplasmic (N/C) ratios of blastomeres reach a critical value during the 13th cycle, their cell cycle durations lengthen in proportion to the reciprocal of cell surface areas, and cell divisions become asynchronous due to variations in cell sizes. The same changes occur in haploid blastomeres with a delay of one cell cycle. Thus, post-MBT cell cycle control becomes dependent not only on the N/C relation but also on cell surface activities of blastomeres. Unlike cell cycle durations of pre-MBT blastomeres, which show monomodal frequency distributions with a peak at about 30 min, those of post-MBT blastomeres show polymodal frequency distributions with peaks at multiples of about 30 min, suggesting 'quantisement' of the cell cycle. Thus, we hypothesised that MPF is produced periodically during its unit cycle with 30 min period, but it titrates, and is neutralized by, an inhibitor contained in the nucleus in a quantity proportional to the genome size; however, when all of the inhibitor has been titrated, excess MPF during the last cycle triggers mitosis. At MBT, cell cycle checkpoint mechanisms begin to operate. While the operation of S phase checkpoint to monitor DNA replication is initiated by N/C relation, the initiation of M phase checkpoint operation to monitor chromosome segregation at mitosis is regulated by an age-dependent mechanism.
Topics: Animals; Cell Cycle; Cell Division; Embryo, Nonmammalian; Xenopus laevis
PubMed: 10068998
DOI: No ID Found -
Medecine Sciences : M/S Feb 2008Cell division is probably the most dramatic event in the life of a cell : the entire genetic material has to be equally distributed into the two daughter cells.... (Review)
Review
Cell division is probably the most dramatic event in the life of a cell : the entire genetic material has to be equally distributed into the two daughter cells. Segregation errors have severe consequences and lead to either cell death or the generation of aneuploid cells and may cause the formation of tumors or tumor promoting mutations in somatic cells. In meiosis, they provoke the generation of aneuploid embryos and/or spontaneous abortions. Trisomies in humans, such as trisomy 21, are due to the missegregation of one chromosome in the first meiotic division in the oocyte. This review deals with the molecular mechanisms regulating the two meiotic divisions required for the generation of female haploid germ cells. Here we focus mainly on spindle assembly, and cell cycle regulation especially during the first meiotic division in mouse oocytes (excellent reviews have been written on the peculiar aspects of cell cycle regulation in meiosis II, such as the CSF arrest).
Topics: Animals; Cell Division; Chromosomes, Human; DNA; Humans; Meiosis; Models, Biological; ran GTP-Binding Protein
PubMed: 18272083
DOI: 10.1051/medsci/2008242197 -
Oncogene May 1999Cell division is coupled to cell growth. Since some c-myc target genes are regulators of cell growth while others function in cell division pathways, c-myc is apparently... (Review)
Review
Cell division is coupled to cell growth. Since some c-myc target genes are regulators of cell growth while others function in cell division pathways, c-myc is apparently poised at the interface of these processes. Cell culture systems have shown specific myc-associated growth phenotypes. Increased cell growth precedes DNA synthesis after myc activation in cells expressing myc-estrogen receptor fuson constructs and cells lacking c-myc exhibit a marked loss of protein synthesis. A number of candidate c-myc target genes regulate processes required for cell growth including rRNA transcription and processing, ribosomal protein transcription and translation, and translation initiation. These interactions all have the potential to account for the growth phenotypes in c-myc mutant cells. The ability of translation initiation factors, including eIF4E, to transform cells makes them particularly interesting targets of c-myc. Further evaluation of these target genes will provide important insights into growth control and c-myc's functions in cellular proliferation.
Topics: Animals; Cell Division; Gene Expression Regulation; Humans; Proto-Oncogene Proteins c-myc
PubMed: 10378694
DOI: 10.1038/sj.onc.1202751