7.6
Centrosome Duplication
The primary microtubule organizing center (MTOC) in animal cells is the centrosome. A centrosome has two cylindrical centrioles at its core. Each cent…
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.
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Q1: What is a centrosome and what role does it play in cell division?
A centrosome is the main microtubule organizing center in eukaryotic cells. It consists of two centrioles surrounded by a pericentriolar matrix and plays a vital role in forming the mitotic spindle, a bipolar arrangement of microtubules that separates sister chromatids during cell division. The two spindle poles are formed by two oppositely placed centrosomes.
Q2: When does centrosome duplication occur during the cell cycle?
Centrosome duplication begins in early G1 phase when separase disengages the two centrioles. Daughter centrioles start growing at a right angle to each parent centriole near S phase onset and elongate through G2. By the time the cell reaches mitosis, it has two centrosomes, each containing a pair of centrioles and pericentriolar matrix.
Q3: What proteins regulate centrosome duplication in the cell cycle?
The G1/S-cyclin dependent kinase complex, consisting of cyclin E and Cdk2 in animal cells, triggers centrosome duplication and cell cycle entry. Plk-4, a polo-like protein kinase, is an important regulator for centriole biogenesis in humans. These proteins ensure centrosome duplication occurs only once per cell cycle.
Q4: How does centrosome duplication resemble chromosome duplication?
Both centrosomes and chromosomes duplicate only once per cell cycle through a semiconservative process where a new copy is produced from a pre-existing parent copy. After cell division, one copy of each is equally distributed to each daughter cell. This parallel regulation ensures proper inheritance of both genetic material and microtubule organizing capacity.
Q5: What happens to centrosomes at the beginning of mitosis?
At mitosis onset, the centrosome splits in two through a process called centrosome disjunction. The two resulting centrosomes move apart, with microtubule motor proteins facilitating their separation. Both centrosomes then nucleate microtubules, primarily at the mother centriole, collectively forming the mitotic spindle and assembly dynein kinesin and microtubules.
Q6: What is the structure of a centriole within a centrosome?
Each centriole consists of nine sets of three microtubules held together by proteins. The two centrioles are positioned at right angles to each other and surrounded by a shapeless protein cloud called the pericentriolar matrix. This organized structure enables the centrosome to function as the primary microtubule organizing center.
Q7: How can excessive centrosome duplication lead to disease?
Excessive centrosome duplication impairs mitotic spindle assembly and causes chromosomes to segregate improperly, leading to chromosomal abnormalities. These errors are implicated in multiple diseases, notably cancer. Tumor suppressor proteins and oncogenes are linked to detrimental changes in tumor cell centrosomes, making them attractive treatment targets.