Of all the processes that permit the existence and perpetuation of life, perhaps the most critical is the ability of cells to accurately duplicate and then faithfully segregate their chromosomes at each cell division. During the cell cycle, a highly regulated process discussed in Chapter 19, cells duplicate their chromosomes precisely once during a period known as S phase (for DNA synthesis phase). Once the individual chromosomes have been duplicated, they are held together by proteins called cohesins. The cells then pass through a period called G₂ (for gap 2) before entering mitosis, the process by which the duplicated chromosomes are segregated to the daughter cells. This process has to be very precise—loss or gain of a chromosome can either be lethal to the cell (in which case it is often not detected) or cause severe complications for the cell. It is estimated that yeast only mis-segregates one of its 16 chromosomes every 100,000 cell divisions, which makes mitosis one of the most accurate processes in biology. To achieve this accuracy, the process must be highly regulated so that it proceeds in an orderly series of steps and errors are not made. The timing and mechanisms that ensure the fidelity of mitosis are closely regulated by the cell cycle circuitry that we discuss in detail in Chapter 19. Here we limit our discussion of this circuitry as it applies to microtubules and the mechanics of mitosis.