Centrosomes Duplicate Early in the Cell Cycle in Preparation for Mitosis
In order to separate the chromosomes during mitosis, cells duplicate their MTOCs—their centrosomes—in a manner coordinated with the duplication of their chromosomes in S phase (Figure 18-36). As we discuss in Chapter 19, the cell cycle is largely driven by the association of cell-cycle-specific cyclins with cyclin-dependent kinases (CDKs). Two kinases—G1/S phase CDKs and another type called Plk4—promote centrosome duplication. The duplicated centrosomes separate as the cells enter mitosis in a process known as centrosome disjunction, and then nucleate the assembly of microtubules to become the two poles of the mitotic spindle. The number of centrosomes in animal cells has to be very carefully controlled. In fact, many tumor cells have more than two centrosomes, which contributes to genetic instability resulting from mis-segregation of chromosomes and hence aneuploidy (unequal numbers of chromosomes). The reasons why aneuploidy results in cancer are discussed in detail in Chapter 24.
FIGURE 18-36 Relation of centrosome duplication to the cell cycle. Centrosome duplication, which is initiated by the G1/S phase CDKs and Plk4 (step 1), results in the pair of centrioles (green) separating and a daughter centriole (blue) budding from each. By the G2 phase, growth of the daughter centrioles is complete, but the two pairs of centrioles remain within a single centrosomal complex. Early in mitosis, driven by the activation of M phase CDKs (step 2), the centrosome splits, each half nucleates assembly of microtubules, and the two centriole pairs are moved to opposite sides of the nucleus. The amount of pericentriolar material and the microtubule nucleation activity of the centrosomes increases greatly in mitosis. In mitosis, each MTOC is called a spindle pole.
As cells enter mitosis, the activity of the two MTOCs—their ability to nucleate microtubules—increases greatly as they accumulate more pericentriolar material. Because the assemblies of microtubules radiating from these two MTOCs now resemble stars, they are often called mitotic asters.