GO:0033301 cell cycle comprising mitosis without cytokinesis: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0033301 describes a mitotic cell cycle in which mitosis completes but cytokinesis fails, producing a multinucleated cell whose nuclei each retain the original ploidy, usually 2N.
• This process is mechanistically distinct from canonical cytokinesis because the contractile ring and abscission machinery are not engaged, even though chromosome segregation and nuclear envelope reformation occur.
• Polo-like kinase 1 (PLK1), Aurora kinases (AURKA/AURKB), and chromosomal passenger complex proteins (INCENP, BIRC5/survivin) are central regulators of the mitotic exit steps that are uncoupled from cytokinesis in this cycle.
• Failure of cytokinesis is a recognized route to tetraploidy and genomic instability, which can promote tumorigenesis and is observed in several cancer types.
• Researchers study GO:0033301 using live-cell imaging, flow cytometry, RNA-seq, and CRISPR-based perturbation of mitotic and cytokinetic genes.
• EDITGENE provides knockout, point-mutation, knock-in, overexpression cell models and CRISPR library screening to dissect the genes controlling mitosis without cytokinesis.
Description
GO:0033301, cell cycle comprising mitosis without cytokinesis, is a biological process in which a cell completes the mitotic program, including chromosome segregation and nuclear division, but does not execute cytokinesis, the physical separation of the cytoplasm. The result is a single cell containing multiple nuclei, each with a chromosomal complement of the original ploidy, typically 2N. This uncoupling of mitosis from cytokinesis is not a rare anomaly; it is a developmentally and pathologically relevant mechanism that generates multinucleated cells in tissues such as placenta, liver, and skeletal muscle, and it is increasingly recognized in cancer biology. Understanding this process is important because it defines a distinct cell-cycle endpoint that affects ploidy, genome stability, and cell fate decisions. Mechanistically, mitosis without cytokinesis requires that the cell exit mitosis normally while suppressing or bypassing the contractile ring assembly and abscission steps that normally follow anaphase. Key mitotic kinases, including PLK1 and Aurora kinases, coordinate chromosome segregation and mitotic exit, and their regulation determines whether cytokinesis is initiated. When cytokinesis fails, the cell can re-enter S phase and become tetraploid, a state that is tolerated in some tissues but can drive genomic instability and tumorigenesis in others. For researchers, GO:0033301 provides a precise ontology term to annotate experiments in which mitosis is completed but cytokinesis is absent. This is critical for interpreting phenotypes in knockout, point-mutation, and overexpression models, and for designing screens that separate mitotic defects from cytokinetic defects. The sections below summarize the definition, mechanism, key genes, disease links, and experimental methods for studying this process.
cell cycle comprising mitosis without cytokinesis At A Glance
| GO ID | GO:0033301 |
|---|---|
| GO term | cell cycle comprising mitosis without cytokinesis |
| Ontology | biological_process |
| Synonym | none |
| Major function | Completion of mitosis without cytokinesis, producing a multinucleated cell with nuclei of original ploidy (usually 2N) |
| Related processes | Mitotic cell cycle, mitotic exit, cytokinesis, contractile ring assembly, abscission |
| Key regulators | PLK1, Aurora kinases (AURKA/AURKB), chromosomal passenger complex (INCENP, BIRC5) |
| Cellular outcome | Multinucleation, tetraploidy, genomic instability |
| Research relevance | Cancer, development, tissue homeostasis, polyploidy |
What Is GO:0033301?
GO:0033301 is defined as a mitotic cell cycle in which mitosis is completed but cytokinesis does not occur, resulting in a cell containing multiple nuclei each with a chromosomal complement of the original ploidy, usually 2N. In other words, the cell successfully segregates its chromosomes and reforms nuclei, but fails to physically divide into two daughter cells, producing a multinucleated cell.
Why Is cell cycle comprising mitosis without cytokinesis Important in Cell Biology?
GO:0033301 is important because it defines a cell-cycle outcome that directly impacts genome stability and cell fate. Cells that complete mitosis without cytokinesis become multinucleated and often tetraploid, a condition that can promote tumorigenesis through chromosomal instability and aneuploidy. In normal development, this process contributes to the formation of syncytia and polyploid tissues, such as placental syncytiotrophoblast and skeletal muscle fibers. Understanding the molecular control of this uncoupling is therefore relevant to cancer biology, developmental biology, and regenerative medicine.
• Provides a precise ontology term for annotating experiments where mitosis completes but cytokinesis fails.
• Links to tetraploidy and genomic instability, which are hallmarks of many cancers.
• Relevant to developmental processes that generate multinucleated cells, such as syncytiotrophoblast formation.
• Helps distinguish mitotic defects from cytokinetic defects in functional screens.
• Key kinases such as PLK1 and Aurora kinases are drug targets, making this process clinically relevant.
• Used in studies of polyploidy in liver, heart, and muscle.
• Provides a framework for understanding how cells can bypass cytokinesis under stress.
• Supports research on cell-cycle checkpoints and mitotic exit.
• Enables comparative analysis of cell division modes across species.
• Informs CRISPR screens aimed at identifying cytokinesis regulators.
What Happens During cell cycle comprising mitosis without cytokinesis?
Mitotic Entry and Chromosome Segregation
In simple terms: The cell starts division and separates its chromosomes normally.
In GO:0033301, the cell enters mitosis and progresses through prophase, metaphase, and anaphase, during which chromosomes are condensed and segregated to opposite poles. This step is driven by cyclin-dependent kinase 1 (CDK1) and Aurora kinases, which ensure bipolar spindle assembly and chromosome bi-orientation. PLK1 also regulates spindle assembly and chromosome segregation. The key feature is that these mitotic events occur normally, setting the stage for nuclear division without subsequent cytokinesis.
Nuclear Envelope Reformation and Nuclear Division
In simple terms: The cell rebuilds nuclei around the separated chromosomes.
After chromosome segregation, nuclear envelopes reform around the two sets of chromosomes, creating two distinct nuclei within a single cell. This step is independent of cytokinesis and is regulated by mitotic exit networks, including the chromosomal passenger complex (CPC) and Aurora B kinase. The CPC, composed of INCENP, BIRC5 (survivin), CDCA8 (borealin), and AURKB, coordinates chromosome segregation and nuclear envelope reformation. In GO:0033301, this nuclear division is completed, but the cell does not divide its cytoplasm.
Suppression or Failure of Cytokinesis
In simple terms: The cell does not split into two daughter cells.
The defining event of GO:0033301 is the absence of cytokinesis. Normally, cytokinesis requires contractile ring assembly, ingression, and abscission, processes that depend on actin, myosin, and vesicle trafficking. In this cycle, these steps are either not initiated or fail, so the cell remains multinucleated. This can occur through downregulation of cytokinetic machinery, inhibition of RhoA signaling, or defects in membrane remodeling. The result is a cell with multiple nuclei, each with a 2N chromosomal complement.
Cell Cycle Re-entry and Polyploidization
In simple terms: The multinucleated cell may continue through the cell cycle and become polyploid.
After completing mitosis without cytokinesis, the multinucleated cell can re-enter the cell cycle, leading to polyploidization or tetraploidy. This re-entry is often associated with genomic instability and can promote tumorigenesis. The decision to re-enter S phase depends on mitotic exit regulators and checkpoint controls, including PLK1 and Aurora kinases. In some developmental contexts, this process is programmed to generate polyploid tissues.
Key Genes Involved in GO:0033301 cell cycle comprising mitosis without cytokinesis
The following genes and proteins are central to the regulation and execution of mitosis without cytokinesis, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PLK1 | Regulates mitotic entry, spindle assembly, and mitotic exit | Target for cancer therapy and cell-cycle studies |
| AURKA | Controls centrosome maturation and spindle assembly | Involved in mitotic regulation and cancer |
| AURKB | Chromosomal passenger complex kinase; regulates chromosome segregation and cytokinesis | Key regulator of mitotic exit and cytokinesis |
| INCENP | Scaffold of chromosomal passenger complex | Essential for Aurora B activation and mitosis |
| BIRC5 (survivin) | Chromosomal passenger complex component; inhibits apoptosis | Links mitosis and apoptosis; cancer target |
| CDCA8 (borealin) | Chromosomal passenger complex component | Required for CPC localization and function |
| RhoA | Regulates contractile ring assembly during cytokinesis | Central to cytokinetic failure studies |
| ECT2 | RhoA guanine nucleotide exchange factor | Controls contractile ring formation |
| ANLN (anillin) | Actin-binding protein in contractile ring | Marker of cytokinetic machinery |
| KIF23 (MKLP1) | Kinesin required for central spindle and abscission | Essential for cytokinesis |
| RACGAP1 | Part of centralspindlin complex | Regulates RhoA during cytokinesis |
| CDK1 | Drives mitotic entry and progression | Master regulator of mitosis |
| CCNB1 (cyclin B1) | Regulatory subunit of CDK1 | Controls mitotic timing |
| ESPL1 (separase) | Cleaves cohesin for chromosome segregation | Required for anaphase |
| TPX2 | Spindle assembly factor | Aurora A activator |
| BUB1 | Spindle assembly checkpoint kinase | Ensures chromosome segregation fidelity |
| MAD2L1 | Spindle assembly checkpoint component | Monitors kinetochore attachment |
How Is cell cycle comprising mitosis without cytokinesis Regulated?
The process of mitosis without cytokinesis is regulated at multiple levels. Mitotic kinases, including CDK1, PLK1, and Aurora kinases, control the timing of mitotic entry and exit, and their activity must be downregulated for mitotic exit to occur. The chromosomal passenger complex (CPC) regulates chromosome segregation and the localization of cytokinetic factors, and its disruption can uncouple mitosis from cytokinesis. Cytokinesis itself is regulated by RhoA signaling, which controls contractile ring assembly; failure to activate RhoA or its effectors leads to cytokinetic failure. Additionally, vesicle trafficking and membrane remodeling are required for abscission, and defects in these processes can result in multinucleation. Transcriptional programs also play a role, as cell cycle-regulated transcription of mitotic genes influences the fidelity of mitosis and cytokinesis.
cell cycle comprising mitosis without cytokinesis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PLK1 | Cancer; mitotic dysregulation | Knockout or point-mutation in cancer cell lines |
| AURKA | Cancer; centrosome amplification | Overexpression or knockout in HeLa cells |
| AURKB | Cancer; cytokinesis failure | Knockout in HCT116 cells |
| BIRC5 | Cancer; apoptosis and mitosis | Overexpression in breast cancer models |
| RhoA | Cytokinesis failure; cancer | Point mutation in RhoA GTPase domain |
Cancer and Genomic Instability
Failure of cytokinesis leading to multinucleation and tetraploidy is a known driver of genomic instability in cancer. Overexpression or dysregulation of PLK1 and Aurora kinases is observed in many tumors and is associated with poor prognosis. Tetraploid cells can undergo further chromosomal instability, contributing to aneuploidy and tumor progression. Targeting mitotic kinases with inhibitors is an active area of cancer therapy.
Developmental Disorders and Polyploid Tissues
Programmed mitosis without cytokinesis is essential for the formation of syncytial tissues, such as the placental syncytiotrophoblast and skeletal muscle fibers. Disruption of this process can lead to developmental defects, including placental insufficiency and muscle abnormalities. Understanding the molecular control of this process is therefore relevant to developmental biology and regenerative medicine.
Neurodegeneration and Aging
Aberrant cell cycle re-entry and multinucleation have been observed in post-mitotic neurons under neurodegenerative conditions, although the role of GO:0033301 in this context is less defined. Further research is needed to establish causal links between mitosis without cytokinesis and neurodegeneration.
From cell cycle comprising mitosis without cytokinesis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate mitosis without cytokinesis? | Knockout cell model (e.g., CRISPR KO) |
| Does a specific mutation in gene X cause cytokinetic failure? | Point-mutation knock-in model |
| Does overexpression of gene X induce multinucleation? | Overexpression cell model |
| Where does protein X localize during mitosis without cytokinesis? | Tagged knock-in (e.g., GFP) |
| Which genes are essential for cytokinesis? | CRISPR library screening |
| What transcriptional changes occur during multinucleation? | RNA-seq in KO vs wild-type |
How to Study the cell cycle comprising mitosis without cytokinesis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Mitosis and cytokinesis dynamics | Confirming GO:0033301 phenotype |
| Flow cytometry | DNA content and ploidy | Detecting tetraploid cells |
| RNA-seq | Transcriptional changes | Identifying pathways in multinucleated cells |
| Phosphoproteomics | Kinase substrate phosphorylation | Mapping PLK1/Aurora signaling |
| CRISPR knockout screening | Gene essentiality for cytokinesis | Identifying novel regulators |
| Immunofluorescence | Protein localization during mitosis | Visualizing CPC and spindle |
| Time-lapse microscopy | Cell division outcome | Tracking cytokinetic failure |
| Western blot | Protein expression and modification | Validating kinase activity |
Live-Cell Imaging
Live-cell imaging with fluorescently labeled chromosomes and membranes allows direct observation of mitosis and cytokinesis in real time, distinguishing cells that complete mitosis without cytokinesis. This method is essential for confirming the GO:0033301 phenotype.
Flow Cytometry and Ploidy Analysis
Flow cytometry can measure DNA content to identify tetraploid or polyploid populations resulting from mitosis without cytokinesis. This is a quantitative method to assess the outcome of cytokinetic failure.
Transcriptomics and RNA-seq
RNA-seq can reveal transcriptional changes associated with multinucleation and cell cycle re-entry, providing insights into the regulatory networks of GO:0033301.
Proteomics and Phosphoproteomics
Mass spectrometry-based proteomics can identify phosphorylation events mediated by PLK1 and Aurora kinases during mitosis without cytokinesis.
How CRISPR Can Be Used to Study GO:0033301 cell cycle comprising mitosis without cytokinesis
Knockout
CRISPR knockout of genes such as PLK1, AURKB, or RhoA can induce mitosis without cytokinesis, allowing researchers to study the loss-of-function phenotype. Knockout cell models are essential for validating gene function in this process.
Point Mutation
Point mutations in kinase domains or GTPase domains (e.g., RhoA) can be introduced to dissect specific residues required for cytokinesis without affecting mitosis. These models help distinguish catalytic from scaffolding functions.
Knock-in
Knock-in of fluorescent tags (e.g., GFP) into endogenous loci allows real-time visualization of protein localization during mitosis without cytokinesis. This is valuable for tracking CPC components and cytokinetic factors.
Overexpression
Overexpression of Aurora kinases or PLK1 can drive multinucleation and tetraploidy, modeling the oncogenic consequences of their dysregulation. Overexpression models are useful for studying gain-of-function effects.
How EDITGENE Supports cell cycle comprising mitosis without cytokinesis Research
Researchers studying cell cycle comprising mitosis without cytokinesis-related genes often need to determine whether a candidate gene is causally involved in the process or merely correlated with it. This requires precise genetic perturbation, which is best achieved through CRISPR-based models that can knockout, mutate, tag, or overexpress the gene of interest in relevant cell types.
Contact EDITGENE today to design your custom CRISPR model for cell cycle comprising mitosis without cytokinesis research.
Frequently Asked Questions About cell cycle comprising mitosis without cytokinesis
What is GO:0033301?
GO:0033301 is a Gene Ontology term for a mitotic cell cycle in which mitosis is completed but cytokinesis does not occur, resulting in a multinucleated cell with nuclei of original ploidy (usually 2N).
What genes are involved in cell cycle comprising mitosis without cytokinesis?
Key genes include PLK1, AURKA, AURKB, INCENP, BIRC5, CDCA8, RhoA, ECT2, ANLN, KIF23, and RACGAP1.
How is mitosis without cytokinesis different from normal cell division?
In normal cell division, cytokinesis follows mitosis to split the cytoplasm; in GO:0033301, cytokinesis fails or is suppressed, leaving a multinucleated cell.
What diseases are associated with mitosis without cytokinesis?
It is associated with cancer and genomic instability, and it occurs in developmental polyploid tissues.
What methods are used to study mitosis without cytokinesis?
Live-cell imaging, flow cytometry, RNA-seq, proteomics, and CRISPR screens are commonly used.
Can CRISPR be used to study mitosis without cytokinesis?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools to dissect gene function in this process.
What is the role of PLK1 in mitosis without cytokinesis?
PLK1 regulates mitotic entry, spindle assembly, and mitotic exit, and its dysregulation can lead to cytokinetic failure.
What is the role of Aurora kinases in this process?
Aurora kinases control chromosome segregation and cytokinesis, and their inhibition can uncouple mitosis from cytokinesis.
How does multinucleation lead to cancer?
Multinucleation and tetraploidy can cause chromosomal instability and aneuploidy, which are hallmarks of cancer.
What cell models are available for studying GO:0033301?
Knockout, point-mutation, knock-in, and overexpression cell models can be generated using CRISPR technology.
Conclusion
GO:0033301, cell cycle comprising mitosis without cytokinesis, is a distinct biological process with important implications for genome stability, development, and disease. Its study requires precise genetic tools to dissect the roles of mitotic kinases, chromosomal passenger complex proteins, and cytokinetic machinery. CRISPR-based models, combined with imaging and omics methods, provide a robust framework for understanding this process. EDITGENE offers comprehensive services to support such research, from knockout and point-mutation models to library screening and bioinformatics.
References
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- 3. Ruchaud S et al.. 2007. Chromosomal passengers: conducting cell division.. Nat Rev Mol Cell Biol 8(10):798-812 PMID: 17848966
- 4. Imoto Y et al.. 2011. The cell cycle, including the mitotic cycle and organelle division cycles, as revealed by cytological observations.. J Electron Microsc (Tokyo) 60 Suppl 1:S117-36 PMID: 21844584
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- 7. Bavetsias V et al.. 2015. Aurora Kinase Inhibitors: Current Status and Outlook.. Front Oncol 5:278 PMID: 26734566
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