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Dr. Boveri's dilemma

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    Dr. Boveri's dilemma

    Um nur mal eine aktuelle Veröffentlichung im Kontext der Aneuploidie-Theorie anzusprechen
    und damit aufzuzeigen, dass wir wirklich die alten Schlachtordungen verlassen sollten

    (also hier:
    Wenn deine Ploidie nicht stimmt, hast du schlechte Karten;
    wenn deine Ploidie aber stimmt, wirst du nie Probleme haben -
    s. Dr. Bliemeister in dem bisher unwidersprochen gebliebenenen BPS-Magazin-Artikel),

    hier der Abstract 1079 des gegenwärtig ablaufenden Treffens der Amerikanischen Society für Zell-Biologie in San Francisco:


    1079

    Interphase fission maintains genomic integrity after failure of cytokinesis in human cells.

    A. Choudhary1, R. Lera1, M. Martowicz1, J. Laffin2, B. Weaver3, M. E. Burkard1;

    1Medicine, University of Wisconsin, Madison, WI,
    2Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, WI,
    3Cell and Regenerative Medicine, University of Wisconsin, Madison, WI

    The century-old Boveri hypothesis predicts that failure of cytokinesis leads to aberrant cell
    divisions, aneuploidy, and cancer. We used modern single-cell techniques to investigate the
    fate of human epithelial cells after failed cytokinesis. To do this, we established a uniform
    population of binucleate interphase RPE1 cells that had previously segregated chromosomes
    (karyokinesis) but failed to divide into daughters (failed cytokinesis). After minimizing effects of
    DNA damage, we found a third of binucleate cells generate viable progeny. Strikingly, the
    majority of the progeny are euploid, with a karyotype that matches the parental line, and only a
    small fraction are near tetraploid. We performed confirmatory experiments that unambiguously
    demonstrate that euploid colonies are derived from single binucleate cells. To elucidate the
    mechanism of this process, we performed timelapse videomicroscopy. This revealed that
    binucleate cells can execute cytoplasmic fission to segregate nuclei without intervening mitosis.
    This fission echoes a primitive adhesion-dependent process reported in lower organisms such
    as Dictyostelia. Using fluorescent Cdt1, we demonstrate that the fission occurs during the G1
    phase. The fission event does not require canonical components required for cytokinesis,
    demonstrating a distinct mechanism. Similar results were found in other human epithelial cell
    types including MCF10a breast epithelial cells and HCT116 colorectal cancer cells. Interphase
    fission can explain previous reports that polyploid multinucleate hepatocytes can resolve to
    euploid hepatocytes. We conclude that human cells have a failsafe mechanism to maintain
    euploidy in the face of cytokinesis failure, making subsequent aneuploidy less frequent than
    envisioned by Boveri.


    human cells have a failsafe mechanism = also ein Fehlerbehebungs-Programm o.ä. - sprich,
    wenns Probleme bei der Zellteilung gibt und dann die Kern/-Chromosom-Situation bei den neuen Zellen nicht stimmt,
    kann das in der Folge ausgeglichen werden und "Euploidy" wieder hergestellt werden, was zu weniger Aneuploidie führt als von Boveri noch angenommen.

    Aber bis jetzt hat sich ja leider keiner der DNA-Zytometriker auf eine Debatte von Boveri & Co. eingelassen - vielleicht macht es ja Udo?

    #2

    Hier noch aus den ASCB-News zu dieser Studie:


    Testing a century-old hypothesis about aneuploidy and cancer reveals

    an ancient failsafe mechanism that may help prevent cancer

    I t takes a whole lot of cell division to grow a human from a single fertilized egg.
    Indeed, it takes an estimated 10hoch13 mitotic cycles, a number about 25 times the number of stars in our galaxy. Beyond number, accuracy also counts in mitosis. This was an early concern of Theodor Boveri, the German cell biology pioneer who in 1914 published his hypothesis that mistakes while dividing up chromosomes in human cells during the mitotic cell cycle would lead to aneuploidy, that is, either too many or too few chromosomes in the resulting daughter cells. Such abnormal cells, Boveri believed, would lead to out-of-control cell division that is a hallmark of cancer.

    In the nearly 100 years since, cell biologists have found considerable evidence that aneuploidy can promote the transformation of normal cells into cancer. But until the recent arrival of live single-cell videomicroscopy techniques, it wasn’t possible to examine a key feature of Boveri’s theory: that aneuploidy results from the failure of cytokinesis, the separation of the cell membrane between segregated chromosomes to form two daughter cells.

    To put Boveri to the single-cell test, Mark Burkard and colleagues at the University of Wisconsin worked with human retinal pigment epithelial (RPE) cells. The researchers allowed the RPE cells to undergo karyokinesis, the orderly separation of chromosomes in mitosis, but blocked cytokinesis, the actual division into two daughter cells. This process resulted in single cells with two nuclei, termed binucleate.

    Binucleate cells were allowed to go through more mitotic cycles and proliferate.To the surprise of the researchers, a third of the binucleate cells generated
    healthy daughter colonies. Moreover, the majority of their progeny had chromosome sets that perfectly matched the original first-generation RPE cell. “This made Boveri’s random chromosome assortment seem rather improbable,” Burkard explains,“so we carefully observed the cells by timelapse microscopy.”

    It turned out that cells with two nuclei got stuck in the first growth phase of the cell cycle long enough to stretch apart, dividing the cytoplasm into two cells, each with its own nucleus. The process neatly preserved the accurately separated chromosome sets. Further work showed that these cells managed to divide without the usual proteins required for division of cell membranes in cytokinesis.

    “We concluded that we were observing a new type of cell division, which we term ‘klerokinesis.’ Klerokinesis is derived from the Greek root for allotted inheritance, chosen because each daughter inherits a full set of chromosomes. Klerokinesis is a primitive mechanism of cell division that appears to be preserved in humans, as similar divisions have been observed in organisms such as slime molds.” Burkard believes that klerokinesis could be an evolutionary failsafe mechanism, critical in rescuing a range of cell functions, from embryonic development to genetic repair. “We hope to learn how to promote klerokinesis to help prevent cancer,” he says

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