“It Takes Two to Tango”: understanding how centrosome duplication is regulated throughout the cell cycle

The essence of successful mitosis is the generation of two genetically identical daughter cells. This requires the assembly of a strictly bipolar mitotic apparatus that will ensure that all daughter chromosomes are segregated to opposite sides of the cell before the completion of mitosis. The agent of the higher animal cell for the establishment of this essential “twoness” is the pair of centrosomes that organize the spindle poles during mitosis (Mazia 1987).

Before the cell enters mitosis, the single interphase centrosome duplicates or reproduces exactly once, and the daughter centrosomes form the two poles of the spindle after breakdown of the nuclear envelope. Failure of the cell to precisely control this duplication of the centrosome can have disastrous consequences. If the centrosome fails to duplicate before the onset of mitosis, most somatic cells eventually return to interphase without dividing, which causes polyploidy. If the centrosome duplicates more than once in a cell cycle, then a multipolar spindle may be assembled and the chromosomes may be unequally distributed to the daughter cells, leading to genetic imbalances that produce cells with aggressive growth characteristics (for reviews, see Orr-Weaver and Weinberg 1998; Brinkley 2001). In fact, the cells of many lethal human tumors are genetically unstable and have abnormally high numbers of centrosomes (Lingle et al. 1998;Pihan et al. 1998; Carroll et al. 1999). Extra centrosomes are a problem because the condition is not remediated; cells do not have a checkpoint that aborts mitosis in response to extra spindle poles (Sluder et al. 1997). In this review, we focus on the mechanisms that control centrosome duplication and coordinate it with nuclear events during the cell cycle.