negative regulation of centrosome duplication

Definition

Target type: biologicalprocess

Any process that decreases the frequency, rate or extent of centrosome duplication. Centrosome duplication is the replication of a centrosome, a structure comprised of a pair of centrioles and peri-centriolar material from which a microtubule spindle apparatus is organized. [GOC:dph, GOC:tb]

Negative regulation of centrosome duplication is a complex process that ensures accurate chromosome segregation during cell division. This process involves a delicate balance of proteins and signaling pathways that control the timing and number of centrosome duplications. Here is a detailed description of the biological process:

**1. Centrosome Licensing:**
* Prior to S phase, the centrosome licensing factor, CDK2, is active and allows the centrosome to become competent for duplication.
* This licensing step is essential to prevent premature duplication.

**2. G1/S Transition:**
* During the transition from G1 to S phase, CDK2 activity decreases, and CDK2 is replaced by CDK2-cyclin E complex.
* The activation of CDK2-cyclin E triggers the initiation of centrosome duplication.

**3. Centrosome Duplication:**
* Centrosome duplication involves the formation of a new centriole next to the existing one.
* The process is mediated by the recruitment and activation of a number of proteins, including PLK1, AURKA, and SAS6.
* These proteins play critical roles in centriole assembly and elongation.

**4. Centrosome Separation:**
* After duplication, the two centrosomes remain connected by microtubules and associated proteins.
* During mitosis, the centrosomes separate and migrate to opposite poles of the cell.
* This separation is facilitated by the action of motor proteins, including dynein and kinesin.

**5. Negative Regulation:**
* The process of centrosome duplication is tightly regulated to ensure that only one duplication event occurs per cell cycle.
* This negative regulation is achieved by a variety of mechanisms, including:
* **Phosphorylation:** Phosphorylation events by kinases, such as PLK1 and AURKA, regulate the activity of centrosome duplication proteins.
* **Ubiquitination:** Ubiquitination, a process that targets proteins for degradation, is crucial for controlling the levels of centrosome duplication proteins.
* **Checkpoint Mechanisms:** Checkpoint pathways, such as the spindle assembly checkpoint, ensure that centrosome duplication and chromosome segregation are properly coordinated.
* **Feedback Inhibition:** Once a centrosome has duplicated, it can inhibit the duplication of other centrosomes through feedback mechanisms.

**6. Errors in Centrosome Duplication:**
* Errors in centrosome duplication can lead to abnormal numbers of centrosomes in cells.
* This can result in aneuploidy (abnormal chromosome numbers), which can contribute to cancer development.
* Additionally, abnormal centrosome numbers can disrupt cell division and lead to other cellular defects.

**Overall, negative regulation of centrosome duplication is essential for maintaining genomic stability and proper cell division. The intricate interplay of proteins, signaling pathways, and checkpoint mechanisms ensures that centrosomes duplicate only once per cell cycle, contributing to the accurate segregation of chromosomes and the overall health of the organism.**'
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Proteins (1)

Compounds (6)