-
Cellular and Molecular Life Sciences :... Mar 2007Orderly progression through mitosis is regulated by the anaphase-promoting complex/cyclosome (APC/C), a large multiprotein E3 ubiquitin ligase that targets key mitotic... (Review)
Review
Orderly progression through mitosis is regulated by the anaphase-promoting complex/cyclosome (APC/C), a large multiprotein E3 ubiquitin ligase that targets key mitotic regulators for destruction by the proteasome. APC/C has two activating subunits, Cdc20 and Cdh1. The well-established view is that Cdc20 activates APC/C from the onset of mitosis through the metaphase-anaphase transition, and that Cdh1 does so from anaphase through G1. Recent work, however, indicates that Cdh1 also activates APC/C in early mitosis and that this APC/C pool targets the anaphase inhibitor securin. To prevent premature degradation of securin, the nuclear transport factors Nup98 and Rae1 associate with APC/C(Cdh1)-securin complexes. In late metaphase, when all kinetochores are attached to spindle microtubules and the spindle assembly checkpoint is satisfied, Nup98 and Rae1 are released from these complexes, thereby allowing for prompt ubiquitination of securin by APC/C(Cdh1). This, and other mechanisms by which the catalytic activity of APC/C is tightly regulated to ensure proper timing of degradation of each of its mitotic substrates, are highlighted.
Topics: Anaphase-Promoting Complex-Cyclosome; Animals; Cell Cycle; Humans; Mitosis; Substrate Specificity; Ubiquitin-Protein Ligase Complexes; Vertebrates
PubMed: 17334950
DOI: 10.1007/s00018-007-6443-1 -
Cell Jan 2000
Review
Topics: Animals; DNA; DNA Replication; Embryonic and Fetal Development; Humans; Macromolecular Substances; Mitosis; Proteins
PubMed: 10647933
DOI: 10.1016/s0092-8674(00)81685-2 -
Cells Jun 2020Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function... (Review)
Review
Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions.
Topics: Humans; Mitosis; RNA Splicing Factors; Transcription Factors
PubMed: 32604778
DOI: 10.3390/cells9061554 -
Journal of Thoracic Oncology : Official... Nov 2009
Topics: Antimitotic Agents; Humans; Lung Neoplasms; Mitosis
PubMed: 19861923
DOI: 10.1097/01.JTO.0000361756.09789.56 -
The Journal of Cell Biology Jun 2022Errors in mitosis that cause chromosome missegregation lead to aneuploidy and micronucleus formation, which are associated with cancer. Accurate segregation requires the...
Errors in mitosis that cause chromosome missegregation lead to aneuploidy and micronucleus formation, which are associated with cancer. Accurate segregation requires the alignment of all chromosomes by the mitotic spindle at the metaphase plate, and any misalignment must be corrected before anaphase is triggered. The spindle is situated in a membrane-free "exclusion zone"; beyond this zone, endomembranes (mainly endoplasmic reticulum) are densely packed. We investigated what happens to misaligned chromosomes localized beyond the exclusion zone. Here we show that such chromosomes become ensheathed in multiple layers of endomembranes. Chromosome ensheathing delays mitosis and increases the frequency of chromosome missegregation and micronucleus formation. We use an induced organelle relocalization strategy in live cells to show that clearance of endomembranes allows for the rescue of chromosomes that were destined for missegregation. Our findings indicate that endomembranes promote the missegregation of misaligned chromosomes that are outside the exclusion zone and therefore constitute a risk factor for aneuploidy.
Topics: Anaphase; Aneuploidy; Cell Membrane; Chromosome Segregation; Chromosomes; Endoplasmic Reticulum; Humans; Metaphase; Mitosis; Spindle Apparatus
PubMed: 35486148
DOI: 10.1083/jcb.202203021 -
Cold Spring Harbor Perspectives in... Dec 2010The nucleus is unique amongst cellular organelles in that it contains a myriad of discrete suborganelles. These nuclear bodies are morphologically and molecularly... (Review)
Review
The nucleus is unique amongst cellular organelles in that it contains a myriad of discrete suborganelles. These nuclear bodies are morphologically and molecularly distinct entities, and they host specific nuclear processes. Although the mode of biogenesis appears to differ widely between individual nuclear bodies, several common design principles are emerging, particularly, the ability of nuclear bodies to form de novo, a role of RNA as a structural element and self-organization as a mode of formation. The controlled biogenesis of nuclear bodies is essential for faithful maintenance of nuclear architecture during the cell cycle and is an important part of cellular responses to intra- and extracellular events.
Topics: Biosynthetic Pathways; Cell Nucleus Structures; Inheritance Patterns; Mitosis; RNA
PubMed: 21068152
DOI: 10.1101/cshperspect.a000711 -
International Journal of Molecular... Sep 2022DNA replication is a tightly regulated fundamental process allowing the correct duplication and transfer of the genetic information from the parental cell to the... (Review)
Review
DNA replication is a tightly regulated fundamental process allowing the correct duplication and transfer of the genetic information from the parental cell to the progeny. It involves the coordinated assembly of several proteins and protein complexes resulting in replication fork licensing, firing and progression. However, the DNA replication pathway is strewn with hurdles that affect replication fork progression during S phase. As a result, cells have adapted several mechanisms ensuring replication completion before entry into mitosis and segregating chromosomes with minimal, if any, abnormalities. In this review, we describe the possible obstacles that a replication fork might encounter and how the cell manages to protect DNA replication from S to the next G1.
Topics: DNA Repair; DNA Replication; Mitosis; S Phase
PubMed: 36232633
DOI: 10.3390/ijms231911331 -
Mediators of Inflammation 2015Mitotic catastrophe, as defined in 2012 by the International Nomenclature Committee on Cell Death, is a bona fide intrinsic oncosuppressive mechanism that senses mitotic... (Review)
Review
Mitotic catastrophe, as defined in 2012 by the International Nomenclature Committee on Cell Death, is a bona fide intrinsic oncosuppressive mechanism that senses mitotic failure and responds by driving a cell to an irreversible antiproliferative fate of death or senescence. Thus, failed mitotic catastrophe can promote the unrestrained growth of defective cells, thereby representing a major gateway to tumour development. Furthermore, the activation of mitotic catastrophe offers significant therapeutic advantage which has been exploited in the action of conventional and targeted anticancer agents. Yet, despite its importance in tumour prevention and treatment, the molecular mechanism of mitotic catastrophe is not well understood. A better understanding of the signals that determine cell fate following failed or defective mitosis will reveal new opportunities to selectively target and enhance the programme for therapeutic benefit and reveal biomarkers to predict patient response. This review is focused on the molecular mechanism of mitotic catastrophe induction and signalling and highlights current strategies to exploit the process in cancer therapy.
Topics: Animals; Antineoplastic Agents; Apoptosis; Humans; Mitosis; Neoplasms; Signal Transduction
PubMed: 26491220
DOI: 10.1155/2015/146282 -
Cell Cycle (Georgetown, Tex.) 2015
Topics: Adaptor Proteins, Signal Transducing; CDC2 Protein Kinase; Cell Cycle; Cell Cycle Proteins; Cyclin-Dependent Kinases; Humans; Mitosis; Phosphoproteins; Phosphorylation; Protein Biosynthesis
PubMed: 26496165
DOI: 10.1080/15384101.2015.1084192 -
International Journal of Molecular... Feb 2014When a human cell detects damaged DNA, it initiates the DNA damage response (DDR) that permits it to repair the damage and avoid transmitting it to daughter cells.... (Review)
Review
When a human cell detects damaged DNA, it initiates the DNA damage response (DDR) that permits it to repair the damage and avoid transmitting it to daughter cells. Despite this response, changes to the genome occur and some cells, such as proliferating cancer cells, are prone to genome instability. The cellular processes that lead to genomic changes after a genotoxic event are not well understood. Our research focuses on the relationship between genotoxic cancer drugs and checkpoint adaptation, which is the process of mitosis with damaged DNA. We examine the types of DNA damage induced by widely used cancer drugs and describe their effects upon proliferating cancer cells. There is evidence that cell death caused by genotoxic cancer drugs in some cases includes exiting a DNA damage cell cycle arrest and entry into mitosis. Furthermore, some cells are able to survive this process at a time when the genome is most susceptible to change or rearrangement. Checkpoint adaptation is poorly characterised in human cells; we predict that increasing our understanding of this pathway may help to understand genomic instability in cancer cells and provide insight into methods to improve the efficacy of current cancer therapies.
Topics: Adaptation, Physiological; Antineoplastic Agents; Cell Cycle Checkpoints; Cell Proliferation; DNA Damage; DNA Repair; Genomic Instability; Humans; Mitosis; Neoplasms
PubMed: 24573252
DOI: 10.3390/ijms15033403