Chromosome Bi-orientation, Tension and the Spindle-Assembly Checkpoint

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Background

Bi-orientation of sister chromatids when they attach to the microtubules of the spindle is essential for eukaryotic life. In 1969, Nicklas and Koch observed that tension guides chromosomes into the proper bi-oriented state. This guidance takes time, and can involve the development of incorrect attachments that must be corrected before cell cycle progression to prevent subsequent chromosome mis-segregation and the development of aneuploidy. The window of time in which to correct errors is created by the spindle-assembly checkpoint (also referred to as the mitotic spindle checkpoint). Since the discovery of genes involved in the spindle checkpoint regulatory pathway by the Hoyt and Murray labs in 1991, a flood of hypotheses and models have been proposed for how the mechanics of proper chromosome bi-orientation, namely tension, intersects with spindle-assembly checkpoint cell cycle control, namely a delay in anaphase entry. Evidence that such an intersection exists was firmly established in the classic experiments of Li and Nicklas in 1995.

However, to-date, the field remains unsettled and somewhat opaque with regard to the cellular, biochemical and molecular mechanisms defining the intersection between tension and cell cycle control. This lack of clarity has created a fragmented set of canonical ideas that confounds the debates between different points of view among scientists in the field. In our view, recent technical and intellectual advances have been combined to generate novel compelling experimental observations creating the possibility of finding sturdy routes and connections that may allow us to crossover some of the chasms separating the fragmented canonical ideas in the field.

Our goal for this Research Topic is to promote a full and open discussion and debate, allowing for all viewpoints to be heard, to investigate the question: how the mechanics of chromosome bi-orientation, namely tension, intersects with spindle-assembly checkpoint cell cycle control, namely a delay in the entry into anaphase. We encourage authors to not only put forth their own viewpoint, but to also challenge the views of others based on the available data within our field. With several recent discoveries, and the advancement of new ideas in the last 5-10 years, we especially encourage our colleagues to incorporate and synthesize diverse models from the past with these more recent observations and concepts. Our goal is to stimulate new avenues of thought that can be pursued experimentally in the near future.

Keywords: mitosis, meiosis, cell cycle, mitotic spindle, chromosomes, microtubules, bi-orientation, spindle-assembly checkpoint, spindle checkpoint

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