18.6:
Centrosome Duplication
A centrosome is the main microtubule organizer of a eukaryotic cell and plays a vital role in the formation of the mitotic spindle, a bipolar arrangement of microtubules that separates sister chromatids. The two spindle poles are formed by two oppositely placed centrosomes.
Prior to the cell cycle, however, most animal cells contain only one centrosome in the cytoplasm. The G1/S-cyclin dependent kinase or Cdk complex—consisting of cyclin E and Cdk2 in animal cells—helps trigger centrosome duplication as well as cell cycle entry.
Each centrosome consists of two centrioles, which are encapsulated by a proteinaceous pericentriolar matrix.
The centrosome duplication starts in the early G1 phase when the separase carries out the disengagement of the two centrioles. A protein belonging to the polo-like protein kinase family, Plk-4, is an important regulator for centriole biogenesis in humans.
Near the onset of S phase, a daughter centriole starts growing at a right angle to the base of each centriole.
During G2, the daughter centrioles typically finish elongating. The four centrioles remain close together in the centrosome until the cell enters mitosis.
At the beginning of mitosis, the centrosome splits in two, which is also known as centrosome disjunction. The two resulting centrosomes each contain a pair of centrioles and the pericentriolar matrix. Both centrosomes nucleate a set of microtubules, primarily at the mother centriole, collectively forming the mitotic spindle.
Centrosome and chromosome life cycle are similar in several aspects. Their duplication occurs only once per cycle and both duplicate through a semiconservative process where a new copy is produced from the pre-existing parent copy.
Also, like chromosomes, one copy of the centrosome is equally distributed to each daughter cell after the division.
Excessive centrosome duplication can impair mitotic spindle assembly and cause chromosomes to segregate improperly, which can cause diseases like cancer.
18.6:
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.
Suggested Reading
- Fujita, Hiroki, Yuki Yoshino, and Natsuko Chiba. 2015. “Regulation of the Centrosome Cycle.” Molecular & Cellular Oncology 3 (2). https://doi.org/10.1080/23723556.2015.1075643.
- Nigg, Erich A., and Andrew J. Holland. 2018. “Once and Only Once: Mechanisms of Centriole Duplication and Their Deregulation in Disease.” Nature Reviews Molecular Cell Biology 19 (5): 297–312. https://doi.org/10.1038/nrm.2017.127.