Mitotic catastrophe

Mitotic catastrophe has been defined as either a cellular mechanism to prevent potentially cancerous cells from proliferating or as a mode of cellular death that occurs following improper cell cycle progression or entrance. Mitotic catastrophe can be induced by prolonged activation of the spindle assembly checkpoint, errors in mitosis, or DNA damage and functioned to prevent genomic instability. It is a mechanism that is being researched as a potential therapeutic target in cancers, and numerous approved therapeutics induce mitotic catastrophe. Multiple attempts to specifically define mitotic catastrophe have been made since the term was first used to describe a temperature dependent lethality in the yeast, Schizosaccharomyces pombe, that demonstrated abnormal segregation of chromosomes. The term has been used to define a mechanism of cellular death that occurs while a cell is in mitosis or as a method of oncosuppression that prevents potentially tumorigenic cells from dividing. This oncosuppression is accomplished by initiating a form of cell death such as apoptosis or necrosis or by inducing cellular senescence. One usage of the term mitotic catastrophe is to describe an oncosuppressive mechanism (i.e. a mechanism to prevent the proliferation of cancerous cells and the develop of tumors) that occurs when cells undergo and detect a defective mitosis has occurred. This definition of this mechanism has been described by the International Nomenclature Committee on Cell Death. Under this definition, cells that undergo mitotic catastrophe either senesce and stop dividing or undergo a regulated form of cell death during mitosis or another form of cell death in the next G1 phase of the cell cycle. The function of this mechanism is to prevent cells from accruing genomic instability which can lead to tumorigenesis. When the cell undergoes cell death during mitosis this is known as mitotic death. This is characterized by high levels of cyclin B1 still present in the cell at the time of cell death indicating the cell never finished mitosis.

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