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Centrosome cycle

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From Wikipedia, the free encyclopedia

Centrioles are nine triplets microtubules

See also: Centrosome and Centriole

Diagram of the centrosome cycle.[1]

Centrosomes are the major microtubule organizing centers (MTOC) in mammalian cells.[2] Failure of centrosome regulation can cause mistakes in chromosome segregation and is associated with aneuploidy. A centrosome is composed of two orthogonal cylindrical protein assemblies, called centrioles, which are surrounded by a protein dense amorphous cloud of pericentriolar material (PCM).[3] The PCM is essential for nucleation and organization of microtubules.[3] The centrosome cycle is important to ensure that daughter cells receive a centrosome after cell division. As the cell cycle progresses, the centrosome undergoes a series of morphological and functional changes. Initiation of the centrosome cycle occurs early in the cell cycle in order to have two centrosomes by the time mitosis occurs.

Since the centrosome organizes the microtubules of a cell, it has to do with the formation of the mitotic spindle, polarity and, therefore, cell shape, as well as all other processes having to do with the mitotic spindle.[2] The centriole is the inner core of the centrosome, and its conformation is typically somewhat like that of spokes on a wheel. It has a somewhat different conformation amount different organisms, but its overall structure is similar. Plants, on the other hand, do not typically have centrioles.[4]

The centrosome cycle consists of four phases that are synchronized to the cell cycle. These include: centrosome duplication during the G1 phase and S Phase, centrosome maturation in the G2 phase, centrosome separation in the mitotic phase, and centrosome disorientation in the late mitotic phase—G1 phase.

Centriole synthesis<br>[edit]

Centrioles are generated in new daughter cells through duplication of pre-existing centrioles in the mother cells. Each daughter cell inherits two centrioles (one centrosome) surrounded by pericentriolar material as a result of cell division. However, the two centrioles are of different ages. This is because one centriole originates from the mother cell while the other is replicated from the mother centriole during the cell cycle.<br>It is possible to distinguish between the two preexisting centrioles because the mother and daughter centriole differ in both shape and function.[5]<br>For example, the mother centriole can nucleate and organize microtubules, whereas the daughter centriole can only nucleate.

First, procentrioles begin to form near each preexisting centriole as the cell moves from the G1 phase to the S phase.[6][7][8] During S and G2 phases of the cell cycle, the procentrioles elongate until they reach the length of the older mother and daughter centrioles. At this point, the daughter centriole takes on the characteristics of a mother centriole. Once they reach full length, the new centriole and its mother centriole form a diplosome. A diplosome is a rigid complex formed by an orthogonal mother and newly formed centriole (now a daughter centriole) that aids in the processes of mitosis. As mitosis occurs, the distance between mother and daughter centriole increases until, congruent with anaphase, the diplosome breaks down and each centriole is surrounded by its own pericentriolar material.[6]

Centrosome duplication<br>[edit]

Cell cycle regulation of centrosome duplication

Centrosomes are only supposed to replicate once in each cell cycle and are therefore highly regulated.[9] The centrosome cycle has been found to be regulated by multiple things, including reversible phosphorylation and proteolysis.[2] It also undergoes specific processes in each step of cell division due to the heavy regulation, which is why the process is so efficient.[9]

Centrosome duplication is heavily regulated by cell cycle controls. This link between the cell cycle and the centrosome cycle is mediated by cyclin-dependent kinase 2 (Cdk2). Cdk2 is a protein kinase (an enzyme) known to regulate the cell cycle.[10] There has been ample evidence[11][12][13][14] that Cdk2 is necessary for both DNA replication and centrosome duplication, which are both key events in S phase. It has also been shown[13][15][16] that Cdk2 complexes with both cyclin A and cyclin E and this complex is critical for centrosome duplication.[10] Three Cdk2 substrates have been proposed to be responsible for regulation of centriole duplication: nucleophosmin (NPM/B23), CP110, and MPS1.[3] Nucleophosmin is only found in unreplicated centrosomes and its phosphorylation by Cdk2/cyclin E removes NPM from the centrosomes, initiating procentriole formation.[17][18] CP110 is an important centrosomal protein that is phosphorylated by both mitotic and interphase Cdk/cyclin complexes and is thought to...