Mechanisms required for ensuring the dependency of cell division on completion of such pre-requisite steps have been termed checkpoints. Checkpoints directly monitor the spatial positioning of chromosomes within the spindle and applies this information to regulate the activities of proteins that induce chromosome separation and allow the cell to exit mitosis. The mitotic checkpoint monitors the kinetochore, the point at which chromosomes are attached to the mitotic spindle during cell division, as a means to determine whether chromosomes have achieved metaphase alignment and can delay onset of anaphase for several hours to ensure that the operation is proceeding without error. The evolutionary conservation of the mechanisms as well as the exquisite sensitivity by which they occur attests to the importance of this fundamental process. The nature of the signal that the kinetochore emits when not properly aligned is an area of intense investigation.
Kinetochores generate motive force through interactions with microtubules.
Then, as each chromosome's kinetochore connects to the mitotic spindle, the wait signal from that kinetochore is silenced until no more wait signals are being generated in the cell. At that point, mitosis can proceed. The huBUB's appear to function as sensors that determine whether chromosomes have aligned properly and then relay this information to the global regulatory machinery that specifies mitotic progression. The molecular analysis of the mitotic checkpoint pathway is not merely an important cell biological question but has practical benefits for developing strategies to enhance the effectiveness of anti-mitotic drugs. By designing drugs that selectively cripple the mitotic checkpoint, one would expect that cells would become much more sensitive to the cytotoxic effects of taxol, vinblastine, and a variety of anti-mitotic compounds used in the clinical setting.