35.6 : Centrosome Duplication

The primary microtubule organizing center (MTOC) in animal cells is the centrosome. A centrosome has two cylindrical centrioles at its core. Each centriole consists of nine sets of three microtubules held together by proteins. The centrioles are positioned at right angles to each other and surrounded by a shapeless protein cloud called the pericentriolar matrix, or pericentriolar material (PCM).

To ensure that each daughter cell receives a centrosome after cell division, centrosome duplication begins early in the cell cycle. Centrosome duplication is tightly regulated by cell cycle controls—such as cyclin-dependent kinase 2 (Cdk2)—to prevent it from occurring more than once per cell cycle. Thus, by the time the cell reaches mitosis, it has two centrosomes.

Centrosome duplication coincides with phases of the cell cycle. During the G₁ phase of the cell cycle, the two centrioles in the centrosome separate, a process called centrosome disorientation.

During the G₁ and S phases, centrosomes are duplicated. A new centriole, called a procentriole, begins to form and elongate at the base of each of the two existing centrioles. The procentrioles elongate through S and G₂ until they are as large as the older centrioles. The four centrioles remain close together within the enlarged PCM until the cell enters mitosis.

During the G₂ phase, γ-tubulin and other PCM proteins accumulate in the centrosome, a process called centrosome maturation.

During the transition between the G₂ and M phases, the centrosomes begin to separate. The two mother centrioles become disconnected, and microtubule motor proteins move the two centrosomes apart.

Errors in centrosome regulation can cause abnormalities in the number of chromosomes and centrosomes. Centrosome abnormalities and defects in centrosome cycle progression are implicated in multiple diseases, notably cancer. Tumor suppressor proteins and oncogenes are linked to detrimental changes in tumor cell centrosomes, making these proteins an attractive treatment target.