GO:0007098 centrosome cycle: Centrosome Duplication and Separation, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0007098 centrosome cycle is the cell cycle process that ensures centrosome duplication and separation, and it can operate with considerable independence from other cell cycle events.
• The cycle is classically divided into duplication, maturation, separation, and licensing steps, each coordinated by cell cycle kinases such as CDK1, CDK2, PLK1, and AURKA.
• Centrosome maturation increases microtubule nucleation capacity and is tuned by the cell cycle oscillator, including in Drosophila embryos.
• Centrosome amplification and loss of centrosome cycle control are strongly linked to cancer, developmental defects, and genomic instability.
• Key regulators include PLK4, STIL, SAS6, CEP192, CEP152, AURKA, PLK1, and the PCM scaffold proteins pericentrin and CEP215.
• CRISPR knockout, point mutation, knock-in, and overexpression models are essential to dissect causal roles of centrosome cycle genes in disease.
Description
The centrosome cycle (GO:0007098) is the biological process in which centrosome duplication and separation take place, and it can operate with a considerable degree of independence from other processes of the cell cycle. Because the centrosome is the primary microtubule-organizing center of animal cells, its duplication must be tightly coordinated with the cell cycle to ensure bipolar spindle assembly and faithful chromosome segregation. The cycle is not a single event but a series of temporally ordered steps, including duplication, maturation, separation, and licensing, each controlled by distinct kinase activities and structural proteins. Researchers study GO:0007098 because defects in centrosome duplication or separation produce extra centrosomes, multipolar spindles, and aneuploidy, which are hallmarks of many cancers and developmental disorders. The process is also of interest in developmental biology, where centrosome size and maturation are tuned by the cell cycle oscillator, as shown in Drosophila embryos. Understanding the centrosome cycle therefore requires integrating cell cycle signaling, structural biology, and quantitative imaging.
centrosome cycle At A Glance
| GO ID | GO:0007098 |
|---|---|
| GO term | centrosome cycle |
| Ontology | biological_process |
| Synonym | centrosome organisation; centrosome organization; centrosome organization and biogenesis |
| Major function | Duplication and separation of the centrosome during the cell cycle |
| Independence | Can operate with considerable independence from other cell cycle processes |
| Key regulators | PLK4, STIL, SAS6, CEP192, CEP152, AURKA, PLK1, CDK1, CDK2 |
| Disease relevance | Cancer, developmental disorders, genomic instability |
What Is GO:0007098?
In simple terms, GO:0007098 centrosome cycle is the set of steps by which a cell copies its centrosome and then separates the two copies so that each daughter cell receives one. The QuickGO definition states that it is the cell cycle process in which centrosome duplication and separation takes place, and that the centrosome cycle can operate with a considerable degree of independence from other processes of the cell cycle. This means that centrosome duplication and separation are not merely passive consequences of DNA replication or mitosis; they are actively regulated by dedicated machinery and can be uncoupled from other cell cycle events under experimental or pathological conditions.
Why Is centrosome cycle Important in Cell Biology?
The centrosome cycle is important because it ensures that each dividing cell has the correct number of centrosomes, which is required for bipolar spindle assembly and accurate chromosome segregation. When the cycle is deregulated, cells can acquire extra centrosomes, leading to multipolar spindles, aneuploidy, and tumorigenesis. Centrosome cycle genes are also implicated in developmental disorders and ciliopathies, because the centrosome is the basal body of cilia. In addition, the cycle is a model system for understanding how a subcellular organelle duplicates once and only once per cell cycle, a question with broad relevance to cell biology.
• Ensures bipolar spindle assembly and faithful chromosome segregation.
• Prevents centrosome amplification, a hallmark of many cancers.
• Coordinates with the cell cycle oscillator to control centrosome size and maturation.
• Provides a paradigm for once-per-cell-cycle organelle duplication.
• Links to ciliogenesis because the mother centriole becomes the basal body.
• Involves druggable kinases such as PLK4, AURKA, and PLK1.
• Deregulation causes aneuploidy and genomic instability.
• Relevant to developmental biology and tissue morphogenesis.
• Requires quantitative imaging and proteomics to study.
• Offers targets for cancer therapeutics and diagnostics.
What Happens During centrosome cycle?
Centriole duplication
In simple terms: The cell makes a new centriole next to each existing one.
Centriole duplication begins at the G1/S transition and is initiated by PLK4, which recruits STIL and SAS6 to form a cartwheel structure that templates the new centriole. This step is tightly licensed so that each mother centriole produces only one daughter centriole per cycle. The process is coordinated with DNA replication but can be uncoupled under experimental conditions.
Centrosome maturation
In simple terms: The centrosome grows and becomes better at nucleating microtubules.
Centrosome maturation involves the accumulation of pericentriolar material (PCM) and increased microtubule nucleation capacity as cells approach mitosis. This step is regulated by kinases including AURKA and PLK1, and by scaffold proteins such as pericentrin and CEP192. Recent work in Drosophila embryos shows that centrosome size is tuned by the cell cycle oscillator, linking maturation to developmental timing.
Centrosome separation
In simple terms: The two centrosomes move apart to form the two poles of the spindle.
Centrosome separation occurs in late G2/prophase and requires the disjunction of the two centrosomes, which is driven by Eg5/kinesin-5 and regulated by PLK1 and AURKA. Separation ensures that the two centrosomes can nucleate the bipolar spindle. Failure of separation leads to monopolar or multipolar spindles and chromosome missegregation.
Licensing and once-per-cycle control
In simple terms: A molecular switch prevents the centrosome from duplicating more than once per cycle.
Licensing ensures that centrioles do not reduplicate within the same cell cycle, and it involves the removal or inhibition of duplication factors after S phase. CDK2 activity and PLK4 levels are key determinants of licensing. Loss of licensing control leads to centrosome amplification, a common feature of cancer cells.
Coordination with the cell cycle
In simple terms: The centrosome cycle is timed to match the rest of the cell cycle.
The centrosome cycle is coordinated with the cell cycle by CDK1 and CDK2 activities, which phosphorylate centrosomal substrates at specific transitions. This coordination can be perturbed, and the centrosome cycle can proceed with considerable independence from other cell cycle processes. Such independence is important for understanding how centrosome abnormalities arise in disease.
Key Genes Involved in GO:0007098 centrosome cycle
The following genes and proteins are central to the regulation and execution of the centrosome cycle (GO:0007098).
| Gene | Major Role | Research Relevance |
|---|---|---|
| PLK4 | Master regulator of centriole duplication | Target for centrosome amplification studies |
| STIL | Cartwheel assembly and PLK4 recruitment | Essential for centriole duplication |
| SAS6 | Cartwheel component | Structural basis of centriole formation |
| CEP192 | PCM scaffold and centriole duplication | Regulates centrosome maturation |
| CEP152 | Centriole duplication and PCM recruitment | Links duplication to maturation |
| AURKA | Centrosome maturation and separation | Kinase target in cancer |
| PLK1 | Mitotic centrosome maturation and separation | Druggable regulator |
| CDK1 | Cell cycle coordination of centrosome cycle | Controls mitotic entry |
| CDK2 | Licensing of centriole duplication | Regulates S phase duplication |
| PCNT | Pericentrin, PCM scaffold | Maintains centrosome integrity |
| CEP215 | PCM scaffold protein | Centrosome maturation |
| NEDD1 | Gamma-tubulin recruitment | Microtubule nucleation |
| TUBG1 | Gamma-tubulin, nucleation | Core nucleation component |
| MCPH1 | Centrosome regulation | Microcephaly gene |
| CEP63 | Centriole duplication | Microcephaly and cancer |
| ODF2 | Centriole appendage protein | Ciliogenesis and centrosome function |
| CEP135 | Centriole assembly | Microcephaly and cancer |
How Is centrosome cycle Regulated?
The centrosome cycle is regulated by cell cycle kinases, most notably CDK1, CDK2, PLK1, and AURKA, which phosphorylate centrosomal substrates at specific transitions. PLK4 activity is tightly controlled by autophosphorylation and degradation to ensure once-per-cycle duplication. Centrosome maturation is regulated by the cell cycle oscillator, which tunes centrosome size and PCM recruitment. Licensing factors and ubiquitin-mediated degradation also contribute to preventing reduplication. These regulatory layers ensure that centrosome duplication and separation are coordinated with the cell cycle while retaining a degree of independence.
centrosome cycle and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PLK4 | Cancer, centrosome amplification | Knockout and overexpression cell lines |
| AURKA | Cancer, mitotic defects | Point mutation and inhibitor studies |
| MCPH1 | Microcephaly | Knockout and knock-in models |
| CEP63 | Microcephaly, cancer | Knockout and tagged knock-in |
| CEP135 | Microcephaly | Knockout and rescue models |
Cancer and genomic instability
Centrosome amplification is a common feature of many cancers and is associated with aneuploidy and tumor progression. Deregulation of PLK4, AURKA, and PLK1 can drive extra centrosomes, multipolar spindles, and chromosome missegregation. Targeting centrosome cycle kinases is therefore an active area of cancer therapeutic research.
Developmental disorders and microcephaly
Mutations in centrosome cycle genes such as MCPH1, CEP63, and CEP135 cause microcephaly and other developmental defects. These disorders highlight the importance of centrosome function in neural progenitor proliferation and brain development.
Ciliopathies
Because the mother centriole becomes the basal body of cilia, defects in the centrosome cycle can lead to ciliopathies affecting kidney, retina, and other tissues. This links GO:0007098 to a broad spectrum of human genetic diseases.
From centrosome cycle-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does PLK4 overexpression cause centrosome amplification? | Overexpression cell model |
| Is AURKA kinase activity required for centrosome maturation? | Point mutation (kinase-dead) knock-in |
| Does loss of CEP192 disrupt PCM recruitment? | Knockout cell line |
| Where does PLK4 localize during the cell cycle? | Tagged knock-in (fluorescent tag) |
| Does MCPH1 mutation cause microcephaly phenotypes? | Knockout and patient-derived cells |
| Can centrosome cycle genes be screened for synthetic lethality? | CRISPR library screening |
How to Study the centrosome cycle Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Fluorescence microscopy | Centrosome number, size, and localization | Duplication and separation assays |
| Live-cell imaging | Dynamics of centrosome cycle | Tracking tagged proteins |
| Proteomics | Centrosomal protein composition | Interactome mapping |
| CRISPR knockout | Gene function loss | Causal testing of regulators |
| CRISPR point mutation | Kinase activity and phospho-sites | Mechanistic studies |
| CRISPR knock-in | Endogenous tagging and reporters | Localization and dynamics |
| CRISPR library screening | Synthetic lethality and modifiers | Cancer target discovery |
Quantitative imaging of centrosomes
Fluorescence microscopy with centriole and PCM markers is the primary method to visualize duplication, maturation, and separation. Live-cell imaging using tagged proteins allows tracking of centrosome dynamics across the cell cycle.
Proteomics of the centrosome
Mass spectrometry-based proteomics has identified numerous centrosomal components and their post-translational modifications. Proximity labeling can map the centrosome interactome in a cell cycle-dependent manner.
Genetic perturbation and CRISPR screens
CRISPR knockout and point mutation models are used to test the function of centrosome cycle genes. Library screening can identify synthetic lethal interactions with centrosome amplification.
Cell cycle synchronization and analysis
Synchronization methods combined with flow cytometry and immunoblotting allow stage-specific analysis of centrosome cycle regulators. This is essential to distinguish duplication, maturation, and separation defects.
How CRISPR Can Be Used to Study GO:0007098 centrosome cycle
Knockout
CRISPR knockout of centrosome cycle genes such as PLK4, STIL, or CEP192 is used to test their requirement for duplication and maturation. Knockout cell lines can be analyzed by imaging and proteomics to define loss-of-function phenotypes.
Point Mutation
Point mutation knock-in of kinase-dead or phospho-deficient alleles allows precise dissection of AURKA, PLK1, or PLK4 function without confounding effects of protein loss. These models are valuable for linking specific phosphorylation events to centrosome cycle steps.
Knock-in
Tagged knock-in of centrosomal proteins with fluorescent or affinity tags enables live-cell imaging and proteomic pull-downs under endogenous regulation. This approach preserves physiological expression levels and is ideal for studying dynamic localization.
Overexpression
Overexpression of PLK4 or AURKA is widely used to induce centrosome amplification and to model cancer-associated phenotypes. Such models help identify downstream consequences of deregulated centrosome cycle control.
How EDITGENE Supports centrosome cycle Research
Researchers studying centrosome cycle-related genes often need to determine whether a candidate gene is causally involved in duplication, maturation, or separation, and how its mutation contributes to disease. EDITGENE provides the full suite of CRISPR cell model services to enable these studies.
Contact EDITGENE today to design your custom CRISPR model for centrosome cycle research.
Frequently Asked Questions About centrosome cycle
What is the centrosome cycle GO:0007098?
GO:0007098 is the biological process in which centrosome duplication and separation takes place, and it can operate with considerable independence from other cell cycle processes.
What are the main steps of the centrosome cycle?
The main steps are centriole duplication, centrosome maturation, centrosome separation, and licensing, each regulated by cell cycle kinases.
What genes are involved in the centrosome cycle?
Key genes include PLK4, STIL, SAS6, CEP192, CEP152, AURKA, PLK1, CDK1, CDK2, PCNT, and CEP215.
How is the centrosome cycle regulated?
It is regulated by CDK1, CDK2, PLK1, and AURKA, which phosphorylate centrosomal substrates at specific cell cycle transitions.
Why is the centrosome cycle important in cancer?
Deregulation causes centrosome amplification, multipolar spindles, and aneuploidy, which are common in cancer.
What diseases are linked to centrosome cycle defects?
Cancer, microcephaly, and ciliopathies are linked to defects in centrosome cycle genes.
How do researchers study the centrosome cycle?
They use fluorescence microscopy, live-cell imaging, proteomics, and CRISPR perturbation.
Can CRISPR be used to study centrosome cycle genes?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to dissect gene function.
What is centrosome maturation?
Centrosome maturation is the accumulation of pericentriolar material and increased microtubule nucleation capacity before mitosis.
How does the centrosome cycle differ from the cell cycle?
The centrosome cycle can operate with considerable independence from other cell cycle processes, although it is normally coordinated with them.
Conclusion
The centrosome cycle (GO:0007098) is a fundamental biological process that ensures proper centrosome duplication and separation, with critical roles in spindle assembly, chromosome segregation, and development. Its deregulation is linked to cancer, microcephaly, and ciliopathies, making it a rich area for mechanistic and translational research. Advances in imaging, proteomics, and CRISPR-based perturbation continue to reveal how this cycle is controlled and how it can be targeted therapeutically.
References
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- 3. Schatten H. 2022. The Centrosome Cycle within the Cell Cycle.. Adv Anat Embryol Cell Biol 235:17-35 PMID: 36525108
- 4. Lukasiewicz KB et al.. 2009. Aurora A, centrosome structure, and the centrosome cycle.. Environ Mol Mutagen 50(8):602-19 PMID: 19774610
- 5. Nigg EA et al.. 2014. The centrosome duplication cycle in health and disease.. FEBS Lett 588(15):2366-72 PMID: 24951839
- 6. Doxsey S et al.. 2005. Centrosome control of the cell cycle.. Trends Cell Biol 15(6):303-11 PMID: 15953548
- 7. Wong SS et al.. 2024. Regulation of centrosome size by the cell-cycle oscillator in Drosophila embryos.. EMBO J 43(3):414-436 PMID: 38233576
- 8. Palazzo RE et al.. 2000. Centrosome maturation.. Curr Top Dev Biol 49:449-70 PMID: 11005031
