Small Molecules as Probes for Biological Processes

It is clear from observing chromosome movements that cell division occurs in an ordered sequence of events (Fig. 2.1-l(a)). Chromosomes attach to spindle microtubule fibers and move to the spindle equator before sister 

The identification of genetic mutations that abolished the benomyl-induced mitotic arrest provided evidence for a feedback mechanism that delays anaphase onset until completion of spindle assembly, now often referred to as the mitotic spindle checkpoint. The names Mad, for mitotic arrest deficient, and Bub, for budding uninhibited by benomyl, were used for 

Mutant cell defective in feedback control fails to arrest 

Experiments examining the intracellular localization of Mad2 have suggested a model for how the feedback control mechanism might operate [38, 39]. At early stages of mitosis, Mad2 localizes to the kinetochore, a structure that forms on each chromosome and mediates attachment to spindle microtubules. As 

Inhibitors of Eg5 are currently in development as anticancer drugs because, like taxol and the vinca alkaloids, they arrest cells in mitosis by activating the spindle checkpoint. The efficacy of these drugs, as demonstrated by recent studies, requires a prolonged, checkpoint-dependent mitotic arrest [42, 19]. Drug resistance is conferred by a compromised spindle checkpoint, for example, through reduced expression of Mad2. 

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