Telophase

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Robert L Margolis - One of the best experts on this subject based on the ideXlab platform.

  • delay of hela cell cleavage into interphase using dihydrocytochalasin b retention of a postmitotic spindle and Telophase disc correlates with synchronous cleavage recovery
    Journal of Cell Biology, 1995
    Co-Authors: S N Martineau, Paul R Andreassen, Robert L Margolis
    Abstract:

    The molecular signals that determine the position and timing of the cleavage furrow during mammalian cell cytokinesis are presently unknown. We have studied in detail the effect of dihydrocytochalasin B (DCB), a drug that interferes with actin assembly, on specific late mitotic events in synchronous HeLa cells. When cleavage furrow formation is blocked at 10 microM DCB, cells return to interphase by the criteria of reformation of nuclei with lamin borders, degradation of the cyclin B component of p34cdc2 kinase, and loss of mitosis specific MPM-2 antigens. However, the machinery for cell cleavage is retained for up to one hour into G1 when cleavage cannot proceed. The components retained consist prominently of a "postmitotic" spindle and a Telophase disc, a structure templated by the mitotic spindle in anaphase that may determine the position and timing of the cleavage furrow. Upon release from DCB block, G1 cells proceed through a rapid and synchronous cleavage. We conclude that the mitotic spindle is not inevitably destroyed at the end of mitosis, but persists as an integral structure with the Telophase disc in the absence of cleavage. We also conclude that cell cleavage can occur in G1, and is therefore an event metabolically independent of mitosis. The retained Telophase disc may indeed signal the position of furrow formation, as G1 cleavage occurs only in the position where the retained disc underlies the cell cortex. The protocol we describe should now enable development of a model system for the study of mammalian cell cleavage as a synchronous event independent of mitosis.

  • hypothesis the Telophase disc its possible role in mammalian cell cleavage
    BioEssays, 1993
    Co-Authors: Robert L Margolis, Paul R Andreassen
    Abstract:

    The molecular signals that determine the position and timing of the furrow that forms during mammalian cell cytokinesis are presently unknown. It is apparent, however, that these signals are generated by the mitotic spindle after the onset of anaphase. Recently we have described a structure that bisects the cell during Telophase at the position of the cytokinetic furrow. This structure, the telephase disc, appears to the templated by the motitc spindle during anaphase, and precedes the formation of the cytokinetic furrow. The relationship of the telephase disc to the myosin and actin based furrowing mechanism is discussed here. We propose that the Telophase disc may determine the position and timing of cleavage by recruitment and alignment of myosin.

  • Telophase disc a new mammalian mitotic organelle that bisects Telophase cells with a possible function in cytokinesis
    Journal of Cell Science, 1991
    Co-Authors: P R Andreassen, D K Palmer, M H Wener, Robert L Margolis
    Abstract:

    We have discovered a novel mitosis-specific human autoantigen that arises at the centromeres of prophase chromosomes, but ultimately participates in formation of an organelle that bisects the cell at late anaphase and during Telophase. The organelle, discernible as a three-dimensional disc by confocal microscopy, encompasses the entire midzone diameter, and its distribution survives disassembly of interpolar microtubules by cold temperature treatment and detergent lysis of cells. Cytokinetic furrow contraction proceeds normally in dihydrocytochalasin B (DCB)-treated cells, and antigen distribution in the furrow is unaltered. In DCB, the furrow retracts in early interphase, coincident with loss of normal membrane association with the disc, resulting in the formation of binucleate cells. The midzone disc in both drug-treated and normal cells is present at the correct time and position to play a central role in cytokinesis. By immunocytochemistry, the disc appears to contain myosin but not actin. The position of the disc and the possible presence of myosin suggest that cytokinesis may involve the interaction of the disc organelle with actin in the cell cortex to produce cleavage in mammalian cells.

Scott E Williams - One of the best experts on this subject based on the ideXlab platform.

  • Telophase correction refines division orientation in stratified epithelia
    eLife, 2019
    Co-Authors: Kendall J Lough, Kevin M Byrd, Carlos Patino Descovich, Danielle C Spitzer, Abby J Bergman, Gerard M J Beaudoin, Louis F Reichardt, Scott E Williams
    Abstract:

    During organogenesis, precise control of spindle orientation balances proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events occurring early in mitosis. Here, we identify a novel orientation mechanism which corrects erroneous anaphase orientations during Telophase. The directionality of reorientation correlates with the maintenance or loss of basal contact by the apical daughter. While the scaffolding protein LGN is known to determine initial spindle positioning, we show that LGN also functions during Telophase to reorient oblique divisions toward perpendicular. The fidelity of Telophase correction also relies on the tension-sensitive adherens junction proteins vinculin, α-E-catenin, and afadin. Failure of this corrective mechanism impacts tissue architecture, as persistent oblique divisions induce precocious, sustained differentiation. The division orientation plasticity provided by Telophase correction may enable progenitors to adapt to local tissue needs.

  • Telophase correction refines division orientation in stratified epithelia
    bioRxiv, 2019
    Co-Authors: Kendall J Lough, Kevin M Byrd, Carlos Patino Descovich, Danielle C Spitzer, Abby J Bergman, Gerard M J Beaudoin, Louis F Reichardt, Scott E Williams
    Abstract:

    ABSTRACT During organogenesis, precise control of spindle orientation ensures a proper balance of proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events that occur early in mitosis. Here, we identify a previously uncharacterized orientation mechanism that occurs during Telophase, correcting erroneous oblique orientations that unexpectedly persist into anaphase. The directionality of reorientation—towards either planar or perpendicular—correlates with the maintenance or loss of basal contact by the apical daughter. While the conserved scaffolding protein Pins/LGN is believed to function primarily through initial spindle positioning, we now show it also functions actively during Telophase to reorient oblique divisions toward perpendicular. The ability to undergo Telophase correction is also critically dependent upon an LGN-independent pathway involving the tension-sensitive adherens junction proteins vinculin, a-catenin and afadin, and correction directionality is influenced by local cell density. Failure of this reorientation mechanism impacts tissue architecture, as excessive oblique divisions induce precocious differentiation. The division orientation plasticity provided by Telophase correction may provide a means for progenitors to dynamically respond to extrinsic cues provided by neighboring cells in order to adapt to local tissue needs.

Felix Machin - One of the best experts on this subject based on the ideXlab platform.

  • dna double strand breaks in Telophase lead to coalescence between segregated sister chromatid loci
    Nature Communications, 2019
    Co-Authors: Jessel Ayraplasencia, Felix Machin
    Abstract:

    DNA double strand breaks (DSBs) pose a high risk for genome integrity. Cells repair DSBs through homologous recombination (HR) when a sister chromatid is available. HR is upregulated by the cycling dependent kinase (CDK) despite the paradox of Telophase, where CDK is high but a sister chromatid is not nearby. Here we study in the budding yeast the response to DSBs in Telophase, and find they activate the DNA damage checkpoint (DDC), leading to a Telophase-to-G1 delay. Outstandingly, we observe a partial reversion of sister chromatid segregation, which includes approximation of segregated material, de novo formation of anaphase bridges, and coalescence between sister loci. We finally show that DSBs promote a massive change in the dynamics of Telophase microtubules (MTs), together with dephosphorylation and relocalization of kinesin-5 Cin8. We propose that chromosome segregation is not irreversible and that DSB repair using the sister chromatid is possible in Telophase. The mechanism regulating DNA repair in late anaphase or Telophase is not yet clear. Here authors reveal that DNA double strand breaks in Telophase causes a partial reversal of sister chromosome segregation which could create an opportunity of using the sister for repair in Telophase.

  • dna damage in Telophase leads to coalescence between segregated sister chromatid loci
    bioRxiv, 2018
    Co-Authors: Jessel Ayraplasencia, Felix Machin
    Abstract:

    The generation of DNA double strand breaks (DSBs) pose a high risk for the maintenance of the genome. Cells repair DSBs through two major mechanisms: non-homologous end joining (NHEJ) and homologous recombination (HR). HR is usually preferred when a sister chromatid is available, thus cells have coupled the activity of the cycling dependent kinase (CDK) to the selection of HR (Symington et al. 2014). Paradoxically, there is a window in the cell cycle where CDK is high despite a sister chromatid is not physically available for HR: late anaphase/Telophase. We have here studied in budding yeast the response to DSBs generated in Telophase by means of the radiomimetic drug phleomycin. We first show that phleomycin treatment activates the DNA damage response and leads to a delay in the Telophase-to-G1 transition. Outstandingly, we also found a partial reversion of sister chromatid segregation, which includes approximation of spindle pole bodies (SPBs) and sister centromeres, de novo formation of anaphase bridges, trafficking of DNA back and forth through the cytokinetic plane and events of coalescence between segregated sister telomeres. We importantly show that phleomycin promotes a massive change in the structure and dynamic of mitotic microtubules (MTs), which coincides with dephosphorylation and re-localization of kinesin-5 Cin8. We propose that anaphase is not entirely irreversible and that there could still be a window to repair DSBs using the sister chromatid after segregation.

  • The ribosomal DNA metaphase loop of Saccharomyces cerevisiae gets condensed upon heat stress in a Cdc14-independent TORC1-dependent manner
    2018
    Co-Authors: Emiliano Matos-perdomo, Felix Machin
    Abstract:

    Chromosome morphology in Saccharomyces cerevisiae is only visible at the microscopic level in the ribosomal DNA array (rDNA). The rDNA has been thus used as a model to characterize condensation and segregation of sister chromatids in mitosis. It has been established that the metaphase structure (“loop”) depends, among others, on the condensin complex; whereas its segregation also depends on that complex, the Polo-like kinase Cdc5 and the cell cycle master phosphatase Cdc14. In addition, Cdc14 also drives rDNA hypercondensation in Telophase. Remarkably, since all these components are essential for cell survival, their role on rDNA condensation and segregation was established by temperature-sensitive (ts) alleles. Here, we show that the heat stress (HS) used to inactivate ts alleles (25 ºC to 37 ºC shift) causes rDNA loop condensation in metaphase-arrested wild type cells, a result that can also be mimicked by other stresses that inhibit the TORC1 pathway. Because this condensation might challenge previous findings with ts alleles, we have repeated classical experiments of rDNA condensation and segregation, yet using instead auxin-driven degradation alleles (aid alleles). We have undertaken the protein degradation at lower temperatures (25 ºC) and concluded that the classical roles for condensin, Cdc5, Cdc14 and Cdc15 still prevailed. Thus, condensin degradation disrupts rDNA higher organization, Cdc14 and Cdc5 degradation precludes rDNA segregation and Cdc15 degradation still allows rDNA hypercompaction in Telophase. Finally, we provide direct genetic evidence that this HS-mediated rDNA condensation is dependent on TORC1 but, unlike the one observed in anaphase, is independent of Cdc14.

Mitsuhiro Yanagida - One of the best experts on this subject based on the ideXlab platform.

  • icrf 193 an anticancer topoisomerase ii inhibitor induces arched Telophase spindles that snap leading to a ploidy increase in fission yeast
    Genes to Cells, 2016
    Co-Authors: Norihiko Nakazawa, Rajesh Mehrotra, Orie Arakawa, Mitsuhiro Yanagida
    Abstract:

    ICRF-193 [meso-4,4-(2,3-butanediyl)-bis(2,6-piperazinedione)] is a complex-stabilizing inhibitor of DNA topoisomerase II (topo II) that is used as an effective anticancer drug. ICRF-193 inhibits topo II catalytic activity in vitro and blocks nuclear division in vivo. Here, we examined the effects of ICRF-193 treatment on chromatin behavior and spindle dynamics using detailed live mitotic cell analysis in the fission yeast, Schizosaccharomyces pombe. Time-lapse movie analysis showed that ICRF-193 treatment leads to an elongation of presumed chromatin fibers connected to kinetochores during mid-mitosis. Anaphase spindles begin to arch, and eventually spindle poles come together abruptly, as if the spindle snapped at the point of spindle microtubule overlap in Telophase. Segregating chromosomes appeared as elastic clumps and subsequently pulled back and merged. The snapped spindle phenotype was abolished by microtubule destabilization after thiabendazole treatment, accompanied by unequal chromosome segregation or severe defects in spindle extension. Thus, we conclude that ICRF-193-treated, unseparated sister chromatids pulling toward opposite spindle poles produce the arched and snapped Telophase spindle. ICRF-193 treatment increased DNA content, suggesting that the failure of sister chromatids to separate properly in anaphase, causes the spindle to break in Telophase, resulting in polyploidization.

  • condensin phosphorylated by the aurora b like kinase ark1 is continuously required until Telophase in a mode distinct from top2
    Journal of Cell Science, 2011
    Co-Authors: Norihiko Nakazawa, Rajesh Mehrotra, Masahiro Ebe, Mitsuhiro Yanagida
    Abstract:

    Condensin is a conserved protein complex that functions in chromosome condensation and segregation. It has not been previously unequivocally determined whether condensin is required throughout mitosis. Here, we examined whether Schizosaccharomyces pombe condensin continuously acts on chromosomes during mitosis and compared its role with that of DNA topoisomerase II (Top2). Using double mutants containing a temperature-sensitive allele of the condensin SMC2 subunit cut14 (cut14-208) or of top2, together with the cold-sensitive nda3-KM311 mutation (in β-tubulin), temperature-shift experiments were performed. These experiments allowed inactivation of condensin or Top2 at various stages throughout mitosis, even after late anaphase. The results established that mitotic chromosomes require condensin and Top2 throughout mitosis, even in Telophase. We then showed that the Cnd2 subunit of condensin (also known as Barren) is the target subunit of Aurora-B-like kinase Ark1 and that Ark1-mediated phosphorylation of Cnd2 occurred throughout mitosis. The phosphorylation sites in Cnd2 were determined by mass spectrometry, and alanine and glutamate residue replacement mutant constructs for these sites were constructed. Alanine substitution mutants of Cnd2, which mimic the unphosphorylated protein, exhibited broad mitotic defects, including at Telophase, and overexpression of these constructs caused a severe dominant-negative effect. By contrast, glutamate substitution mutants, which mimic the phosphorylated protein, alleviated the segregation defect in Ark1-inhibited cells. In Telophase, the condensin subunits in cut14-208 mutant accumulated in lumps that contained telomeric DNA and proteins that failed to segregate. Condensin might thus serve to keep the segregated chromosomes apart during Telophase.

  • priming of centromere for cenp a recruitment by human hmis18α hmis18β and m18bp1
    Developmental Cell, 2007
    Co-Authors: Yohta Fujita, Takeshi Hayashi, Tomomi Kiyomitsu, Yusuke Toyoda, Aya Kokubu, Chikashi Obuse, Mitsuhiro Yanagida
    Abstract:

    Summary The centromere is the chromosomal site that joins to microtubules during mitosis for proper segregation. Determining the location of a centromere-specific histone H3 called CENP-A at the centromere is vital for understanding centromere structure and function. Here, we report the identification of three human proteins essential for centromere/kinetochore structure and function, hMis18α, hMis18β, and M18BP1, the complex of which is accumulated specifically at the Telophase-G1 centromere. We provide evidence that such centromeric localization of hMis18 is essential for the subsequent recruitment of de novo-synthesized CENP-A. If any of the three is knocked down by RNAi, centromere recruitment of newly synthesized CENP-A is rapidly abolished, followed by defects such as misaligned chromosomes, anaphase missegregation, and interphase micronuclei. Tricostatin A, an inhibitor to histone deacetylase, suppresses the loss of CENP-A recruitment to centromeres in hMis18α RNAi cells. Telophase centromere chromatin may be primed or licensed by the hMis18 complex and RbAp46/48 to recruit CENP-A through regulating the acetylation status in the centromere.

Kendall J Lough - One of the best experts on this subject based on the ideXlab platform.

  • Telophase correction refines division orientation in stratified epithelia
    eLife, 2019
    Co-Authors: Kendall J Lough, Kevin M Byrd, Carlos Patino Descovich, Danielle C Spitzer, Abby J Bergman, Gerard M J Beaudoin, Louis F Reichardt, Scott E Williams
    Abstract:

    During organogenesis, precise control of spindle orientation balances proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events occurring early in mitosis. Here, we identify a novel orientation mechanism which corrects erroneous anaphase orientations during Telophase. The directionality of reorientation correlates with the maintenance or loss of basal contact by the apical daughter. While the scaffolding protein LGN is known to determine initial spindle positioning, we show that LGN also functions during Telophase to reorient oblique divisions toward perpendicular. The fidelity of Telophase correction also relies on the tension-sensitive adherens junction proteins vinculin, α-E-catenin, and afadin. Failure of this corrective mechanism impacts tissue architecture, as persistent oblique divisions induce precocious, sustained differentiation. The division orientation plasticity provided by Telophase correction may enable progenitors to adapt to local tissue needs.

  • Telophase correction refines division orientation in stratified epithelia
    bioRxiv, 2019
    Co-Authors: Kendall J Lough, Kevin M Byrd, Carlos Patino Descovich, Danielle C Spitzer, Abby J Bergman, Gerard M J Beaudoin, Louis F Reichardt, Scott E Williams
    Abstract:

    ABSTRACT During organogenesis, precise control of spindle orientation ensures a proper balance of proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events that occur early in mitosis. Here, we identify a previously uncharacterized orientation mechanism that occurs during Telophase, correcting erroneous oblique orientations that unexpectedly persist into anaphase. The directionality of reorientation—towards either planar or perpendicular—correlates with the maintenance or loss of basal contact by the apical daughter. While the conserved scaffolding protein Pins/LGN is believed to function primarily through initial spindle positioning, we now show it also functions actively during Telophase to reorient oblique divisions toward perpendicular. The ability to undergo Telophase correction is also critically dependent upon an LGN-independent pathway involving the tension-sensitive adherens junction proteins vinculin, a-catenin and afadin, and correction directionality is influenced by local cell density. Failure of this reorientation mechanism impacts tissue architecture, as excessive oblique divisions induce precocious differentiation. The division orientation plasticity provided by Telophase correction may provide a means for progenitors to dynamically respond to extrinsic cues provided by neighboring cells in order to adapt to local tissue needs.