GO:0010824 regulation of centrosome duplication: Cell Cycle Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0010824 regulation of centrosome duplication describes any process that modulates the frequency, rate or extent of centrosome duplication, the replication of a centrosome from which the microtubule spindle apparatus is organized.
• Centrosome duplication must occur exactly once per cell cycle, and its licensing and execution are controlled by both positive and negative regulators.
• Key regulators include BRCA1, BARD1, RACK1, OLA1, CCDC102A, Sufu, and components of the DNA replication machinery.
• Loss of centrosome duplication control causes centrosome amplification, a hallmark of many cancers and a contributor to chromosomal instability.
• Centrosome duplication-related genes have been proposed as biomarkers in non-cancer diseases such as hypertrophic cardiomyopathy.
• CRISPR knockout, point-mutation, knock-in, and overexpression models are essential for dissecting causal roles of candidate regulators in centrosome duplication.
Description
Regulation of centrosome duplication (GO:0010824) is the biological process that controls the frequency, rate, or extent of centrosome duplication, the replication of a centrosome structure composed of a pair of centrioles and peri-centriolar material. Because the centrosome organizes the microtubule spindle apparatus, its duplication must be tightly coordinated with the cell cycle to ensure bipolar spindle formation and accurate chromosome segregation. Disruption of this regulation leads to centrosome amplification, multipolar spindles, and aneuploidy, which are common features of cancer and other proliferative disorders. Research over the past two decades has identified a network of proteins that either promote or restrain centrosome duplication. BRCA1 and its partner BARD1, together with OLA1 and RACK1, cooperate to suppress centrosome amplification. The DNA replication machinery transmits dual signals that prevent unscheduled licensing and execution of centrosome duplication, coupling S-phase events to centrosome licensing. Negative regulators such as Sufu restrain both centrosome duplication and DNA replication initiation, while CCDC102A has dual roles in governing centrosome duplication and cohesion. Understanding GO:0010824 is therefore central to cell cycle biology, genome stability, and disease mechanisms. This article synthesizes authoritative QuickGO annotation and verified PubMed literature to outline the definition, mechanisms, key genes, disease links, and experimental methods used to study regulation of centrosome duplication.
regulation of centrosome duplication At A Glance
| GO ID | GO:0010824 |
|---|---|
| GO term | regulation of centrosome duplication |
| Ontology | biological_process |
| Synonym | None listed in QuickGO |
| Major function | Modulates the frequency, rate or extent of centrosome duplication, ensuring once-per-cell-cycle replication of the centrosome |
| Related structure | Centrosome, composed of a pair of centrioles and peri-centriolar material |
| Key positive/negative regulators | BRCA1, BARD1, RACK1, OLA1, CCDC102A, Sufu, DNA replication machinery |
| Disease relevance | Centrosome amplification in cancer; candidate biomarkers in hypertrophic cardiomyopathy |
| Research methods | CRISPR KO/point mutation/knock-in/overexpression, imaging, multi-omics, single-cell transcriptomics |
What Is GO:0010824?
GO:0010824 regulation of centrosome duplication is defined as any process that modulates the frequency, rate or extent of centrosome duplication. Centrosome duplication itself 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. In practice, this GO term covers both positive and negative regulatory inputs that ensure centrosome duplication occurs once, and only once, per cell cycle.
Why Is regulation of centrosome duplication Important in Cell Biology?
Regulation of centrosome duplication is essential because the centrosome is the primary microtubule-organizing center of animal cells, and its duplication must be coordinated with DNA replication and cell division. When this regulation fails, cells can acquire extra centrosomes, leading to multipolar spindles, chromosome mis-segregation, and aneuploidy, which drive tumorigenesis and other diseases. Moreover, recent work links centrosome duplication-related genes to non-cancer conditions such as hypertrophic cardiomyopathy, highlighting broader biomedical relevance.
• Ensures once-per-cell-cycle centrosome duplication, preventing centrosome amplification.
• Maintains bipolar spindle formation and accurate chromosome segregation.
• Loss of BRCA1 or BARD1 function causes centrosome amplification and genomic instability.
• RACK1 is a key regulator of centrosome function and is implicated in carcinogenesis.
• CCDC102A coordinates centrosome duplication and cohesion, linking these processes.
• Sufu negatively regulates both centrosome duplication and DNA replication initiation.
• The DNA replication machinery prevents unscheduled centrosome licensing.
• Centrosome duplication-related biomarkers are being explored in hypertrophic cardiomyopathy.
• Dysregulation contributes to aneuploidy, a hallmark of many cancers.
• Provides targets for CRISPR-based functional studies and therapeutic development.
What Happens During regulation of centrosome duplication?
Licensing of centrosome duplication
In simple terms: Before a centrosome can duplicate, it must receive a molecular permission slip.
Centrosome duplication begins with a licensing step that marks the mother centriole for the assembly of a daughter centriole. The DNA replication machinery transmits dual signals that prevent unscheduled licensing and execution of centrosome duplication, ensuring that licensing occurs only once per cell cycle. Negative regulators such as Sufu can restrain this initiation step, preventing premature or extra duplication events.
Initiation and elongation of daughter centrioles
In simple terms: The new centriole starts to form next to the old one and then grows.
After licensing, daughter centriole assembly initiates and elongates. Proteins such as CCDC102A play dual roles in governing centrosome duplication and cohesion, helping to coordinate centriole formation with sister chromatid cohesion. The process is tightly regulated so that each mother centriole templates exactly one daughter centriole per cycle.
Negative regulation and restriction to once per cycle
In simple terms: Brakes are applied so the centrosome does not duplicate again too soon.
Multiple negative regulators prevent re-duplication within the same cell cycle. BRCA1, in cooperation with BARD1, OLA1, and RACK1, suppresses centrosome amplification. Sufu negatively regulates both initiations of centrosome duplication and DNA replication, acting as a dual brake. The DNA replication machinery also provides inhibitory signals that block unscheduled licensing.
Coordination with the cell cycle and DNA replication
In simple terms: Centrosome copying is timed to match DNA copying.
Centrosome duplication is coordinated with DNA replication and cell cycle progression. The DNA replication machinery transmits dual signals to prevent unscheduled licensing and execution of centrosome duplication, coupling S-phase events to centrosome duplication. This coordination ensures that by mitosis, the cell has exactly two centrosomes to form a bipolar spindle.
Centrosome maturation and spindle assembly
In simple terms: The duplicated centrosomes mature and then build the spindle.
After duplication, centrosomes mature by recruiting peri-centriolar material, increasing their microtubule-nucleating capacity. The mature centrosomes then organize the microtubule spindle apparatus, a function that depends on the structural integrity of the centrosome. Proper regulation of duplication is a prerequisite for bipolar spindle assembly and accurate chromosome segregation.
Key Genes Involved in GO:0010824 regulation of centrosome duplication
The following genes and proteins have been experimentally implicated in the regulation of centrosome duplication (GO:0010824) according to verified PubMed literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| BRCA1 | Suppresses centrosome amplification; cooperates with BARD1/OLA1/RACK1 | Breast/ovarian cancer; centrosome duplication control |
| BARD1 | Partners with BRCA1 to regulate centrosome duplication | Cancer susceptibility; centrosome regulation |
| RACK1 | Regulates centrosome function; implicated in carcinogenesis | Cancer biology; centrosome regulation |
| OLA1 | Cooperates with BRCA1/BARD1/RACK1 in centrosome regulation | Centrosome duplication control |
| CCDC102A | Dual roles in centrosome duplication and cohesion | Cell cycle; centrosome cohesion |
| Sufu | Negatively regulates initiation of centrosome duplication and DNA replication | Hedgehog signaling; cell cycle control |
| DNA replication machinery components | Transmit dual signals preventing unscheduled centrosome licensing | S-phase coordination; genome stability |
| Centrin | Structural component of centrioles | Centrosome structure and duplication |
| Pericentrin | Peri-centriolar material component | Centrosome maturation |
| γ-tubulin | Microtubule nucleation at centrosome | Spindle assembly |
| PLK4 | Master regulator of centriole duplication (general knowledge, not cited here) | Centriole biogenesis (not cited in this article) |
| CDK2 | Cell cycle kinase coordinating centrosome duplication (general knowledge, not cited here) | Cell cycle regulation (not cited in this article) |
| BRCA2 | Linked to centrosome regulation (general knowledge, not cited here) | Cancer (not cited in this article) |
| TP53 | Guardian of genome stability (general knowledge, not cited here) | Cancer (not cited in this article) |
| Aurora A | Centrosome maturation kinase (general knowledge, not cited here) | Mitosis (not cited in this article) |
| Cyclin E | S-phase regulator (general knowledge, not cited here) | Cell cycle (not cited in this article) |
| MCPH1 | Centrosome regulation (general knowledge, not cited here) | Microcephaly (not cited in this article) |
| CEP152 | Centriole duplication (general knowledge, not cited here) | Microcephaly (not cited in this article) |
How Is regulation of centrosome duplication Regulated?
Regulation of centrosome duplication is itself controlled by multiple inputs. The DNA replication machinery transmits dual signals that prevent unscheduled licensing and execution of centrosome duplication, linking centrosome duplication to S-phase progression. Sufu acts as a negative regulator of both centrosome duplication initiation and DNA replication initiation. BRCA1, BARD1, OLA1, and RACK1 cooperate to suppress centrosome amplification, forming a regulatory module. CCDC102A further coordinates centrosome duplication with cohesion. These layers ensure that centrosome duplication occurs exactly once per cell cycle.
regulation of centrosome duplication and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| BRCA1 | Breast/ovarian cancer; centrosome amplification | CRISPR KO in cancer cell lines; centrosome imaging |
| BARD1 | Cancer susceptibility; centrosome regulation | Knockout and point-mutation models |
| RACK1 | Carcinogenesis; centrosome regulation | Overexpression and KO models |
| CCDC102A | Cohesion and centrosome duplication defects | Knock-in/knockout with imaging |
| Sufu | Hedgehog-related developmental disorders | KO and overexpression models |
Cancer and centrosome amplification
Centrosome amplification is a common feature of many cancers and contributes to chromosomal instability. Loss of BRCA1 function leads to centrosome amplification, and BRCA1 cooperates with BARD1, OLA1, and RACK1 to regulate centrosome duplication. RACK1 is also implicated in carcinogenesis through its roles in centrosome regulation. Dysregulation of GO:0010824 therefore promotes aneuploidy and tumor progression.
Hypertrophic cardiomyopathy
A recent multi-omics and single-cell transcriptomics study identified centrosome duplication-related biomarkers in hypertrophic cardiomyopathy, suggesting that genes annotated to GO:0010824 may have roles beyond cancer. Experimental validation in that study supports the relevance of these biomarkers in cardiac disease.
Developmental and cohesion disorders
CCDC102A governs both centrosome duplication and cohesion, and its dual roles suggest that disruption could affect chromosome cohesion and cell division. Sufu negatively regulates centrosome duplication and DNA replication, linking this process to Hedgehog signaling pathways that are important in development.
From regulation of centrosome duplication-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of BRCA1 cause centrosome amplification? | CRISPR knockout of BRCA1 in cell lines |
| How does BARD1 cooperate with BRCA1 in centrosome regulation? | Knockout and point-mutation models |
| What is the role of RACK1 in centrosome function? | Overexpression and knockout models |
| How does CCDC102A coordinate duplication and cohesion? | Knock-in/knockout with live imaging |
| Does Sufu negatively regulate centrosome duplication? | Knockout and overexpression models |
| Can centrosome duplication genes serve as biomarkers in cardiomyopathy? | Multi-omics and single-cell transcriptomics with validation |
How to Study the regulation of centrosome duplication Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Fluorescence microscopy | Centrosome number and duplication status | Assessing centrosome amplification |
| Live-cell imaging | Centriole duplication dynamics | Studying CCDC102A and cohesion |
| Single-cell transcriptomics | Gene expression heterogeneity | Biomarker discovery in cardiomyopathy |
| Multi-omics integration | Combined genomic/proteomic profiles | Identifying centrosome duplication biomarkers |
| CRISPR knockout | Loss-of-function effects | Testing BRCA1/BARD1 roles |
| CRISPR knock-in | Tagged or mutant protein expression | Studying CCDC102A dual roles |
| Co-immunoprecipitation | Protein-protein interactions | BRCA1/BARD1/OLA1/RACK1 complex |
| Cell cycle synchronization | Stage-specific centrosome events | Coordinating duplication with S-phase |
Imaging-based assays for centrosome duplication
Fluorescence microscopy of centriolar markers (e.g., centrin, pericentrin) is used to count centrosomes and assess duplication status. Such imaging has been used to show that BRCA1 loss leads to centrosome amplification and to study CCDC102A dual roles.
Multi-omics and single-cell transcriptomics
Integrative multi-omics combined with single-cell transcriptomics has been applied to identify centrosome duplication-related biomarkers in hypertrophic cardiomyopathy, followed by experimental validation. This approach can reveal disease-specific expression patterns of GO:0010824 genes.
CRISPR functional genomics
CRISPR knockout, point-mutation, knock-in, and overexpression models allow causal testing of candidate regulators. For example, knockout of BRCA1 or BARD1 has been used to study centrosome regulation, and the DNA replication machinery has been dissected using genetic approaches.
Biochemical and protein interaction assays
Co-immunoprecipitation and protein interaction studies have revealed cooperation among BRCA1, BARD1, OLA1, and RACK1 in centrosome regulation. Such assays help define the molecular complexes that control GO:0010824.
How CRISPR Can Be Used to Study GO:0010824 regulation of centrosome duplication
Knockout
CRISPR knockout is used to delete candidate regulators such as BRCA1, BARD1, or Sufu to test whether loss of function causes centrosome amplification or unscheduled duplication. Knockout models provide causal evidence for the role of a gene in GO:0010824.
Point Mutation
Point-mutation models introduce specific amino acid changes to dissect functional domains. For example, mutations in BRCA1 or BARD1 can separate their roles in centrosome regulation from other functions. Such models are valuable for understanding mechanism.
Knock-in
Knock-in of tagged or mutant alleles allows visualization and tracking of proteins such as CCDC102A in live cells, revealing dual roles in centrosome duplication and cohesion. Knock-in can also be used to express disease-associated variants.
Overexpression
Overexpression models test whether increased levels of a regulator, such as RACK1 or Sufu, alter centrosome duplication. Overexpression can reveal dominant-negative or gain-of-function effects on GO:0010824.
How EDITGENE Supports regulation of centrosome duplication Research
Researchers studying regulation of centrosome duplication-related genes often need to determine whether a candidate gene is causally involved in controlling centrosome number, licensing, or duplication timing. EDITGENE provides CRISPR-based cell model services that enable precise genetic perturbations to answer these questions.
Contact EDITGENE today to design your custom CRISPR model for regulation of centrosome duplication research.
Frequently Asked Questions About regulation of centrosome duplication
What is GO:0010824 regulation of centrosome duplication?
GO:0010824 is a biological process term describing any process that modulates the frequency, rate or extent of centrosome duplication, the replication of a centrosome from which the microtubule spindle apparatus is organized.
What genes are involved in regulation of centrosome duplication?
Key genes include BRCA1, BARD1, RACK1, OLA1, CCDC102A, and Sufu, as well as components of the DNA replication machinery.
Why is regulation of centrosome duplication important?
It ensures once-per-cell-cycle centrosome duplication, preventing centrosome amplification, multipolar spindles, and aneuploidy, which are linked to cancer and other diseases.
How does BRCA1 regulate centrosome duplication?
BRCA1, in cooperation with BARD1, OLA1, and RACK1, suppresses centrosome amplification and helps restrict duplication to once per cell cycle.
What happens when centrosome duplication is dysregulated?
Dysregulation leads to centrosome amplification, chromosomal instability, and aneuploidy, which are common in cancer.
What is the role of CCDC102A in centrosome duplication?
CCDC102A has dual roles in governing centrosome duplication and cohesion, coordinating these processes.
How does Sufu affect centrosome duplication?
Sufu negatively regulates both initiations of centrosome duplication and DNA replication.
Can centrosome duplication genes be biomarkers for disease?
Yes, centrosome duplication-related biomarkers have been identified in hypertrophic cardiomyopathy through multi-omics and single-cell transcriptomics.
What methods are used to study regulation of centrosome duplication?
Methods include fluorescence microscopy, live-cell imaging, CRISPR knockout/knock-in, multi-omics, and single-cell transcriptomics.
How can CRISPR help study GO:0010824?
CRISPR knockout, point mutation, knock-in, and overexpression models allow causal testing of candidate regulators of centrosome duplication.
Conclusion
GO:0010824 regulation of centrosome duplication is a critical biological process that ensures the centrosome is duplicated exactly once per cell cycle. Its dysregulation leads to centrosome amplification and genomic instability, with strong links to cancer and emerging relevance in hypertrophic cardiomyopathy. Key regulators such as BRCA1, BARD1, RACK1, OLA1, CCDC102A, and Sufu form a complex network that controls licensing, initiation, and restriction of duplication. Continued research using CRISPR models and multi-omics will further clarify these mechanisms and their therapeutic potential.
References
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- 2. Yoshino Y et al.. 2022. Roles of RACK1 in centrosome regulation and carcinogenesis.. Cell Signal 90:110207 PMID: 34843916
- 3. Otsuka K et al.. 2020. The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1.. Genes (Basel) 11(8) PMID: 32722046
- 4. Deng CX. 2002. Roles of BRCA1 in centrosome duplication.. Oncogene 21(40):6222-7 PMID: 12214252
- 5. Matsuhashi K et al.. 2025. The DNA replication machinery transmits dual signals to prevent unscheduled licensing and execution of centrosome duplication.. Nat Commun 16(1):7799 PMID: 40921755
- 6. Zhuang T et al.. 2021. Sufu negatively regulates both initiations of centrosome duplication and DNA replication.. Proc Natl Acad Sci U S A 118(28) PMID: 34260378
- 7. Li H et al.. 2026. Identification of Centrosome Duplication-Related Biomarkers in Hypertrophic Cardiomyopathy Through Integrative Multi-Omics, Single-Cell Transcriptomics, and Experimental Validation.. J Am Heart Assoc 15(12):e047416 PMID: 42261922
- 8. Andersen SS. 1999. Molecular characteristics of the centrosome.. Int Rev Cytol 187:51-109 PMID: 10212978
