GO:0140014 mitotic nuclear division: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0140014 mitotic nuclear division is the biological process by which a eukaryotic nucleus divides, producing two daughter nuclei with identical chromosome complements.
• The process requires chromosome condensation, nuclear envelope and nuclear pore complex disassembly and reassembly, and coordination with cytoplasmic division.
• Mitotic nuclear division can be studied in organisms ranging from yeast to worms to plants, revealing conserved and divergent mechanisms.
• Defects in mitotic nuclear division cause chromosome instability, which can activate innate immune signaling such as the cGAS-STING pathway.
• Nuclear architecture and mitotic memory influence how daughter cells retain gene expression states after division.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) are essential to dissect gene function in mitotic nuclear division.
Description
Mitotic nuclear division (GO:0140014) is a fundamental biological process in which the nucleus of a eukaryotic cell divides, producing two daughter nuclei that are genetically identical to the mother cell. This process is central to growth, development, and tissue homeostasis in all eukaryotes, and its dysregulation is linked to diseases such as cancer and developmental disorders. Researchers study mitotic nuclear division to understand how chromosomes are faithfully segregated, how nuclear structures are remodeled, and how these events are coordinated with cell cycle progression. The process is highly conserved but also exhibits organism-specific features, as shown by studies in Arabidopsis, Caenorhabditis elegans, and fission yeast. Because mitotic errors can lead to chromosome instability and activate immune responses, the molecular players involved are attractive targets for both basic research and therapeutic development. This article provides a research-grade overview of the ontology, mechanisms, key genes, and experimental approaches for studying GO:0140014.
mitotic nuclear division At A Glance
| GO ID | GO:0140014 |
|---|---|
| GO term | mitotic nuclear division |
| Ontology | biological_process |
| Synonym | mitosis |
| Definition | A mitotic cell cycle process comprising the steps by which the nucleus of a eukaryotic cell divides; involves condensation of chromosomal DNA into a highly compacted form, producing two daughter nuclei with identical chromosome complement. |
| Major function | Segregation of duplicated chromosomes into two daughter nuclei during mitosis. |
| Related processes | Chromosome condensation, nuclear envelope breakdown and reassembly, nuclear pore complex disassembly and reassembly, cytokinesis. |
| Taxonomic range | Eukaryotes, including animals, plants, and fungi. |
| Disease relevance | Chromosome instability, cancer, and innate immune activation via cGAS-STING. |
What Is GO:0140014?
According to the Gene Ontology, GO:0140014 mitotic nuclear division is a mitotic cell cycle process comprising the steps by which the nucleus of a eukaryotic cell divides; the process involves condensation of chromosomal DNA into a highly compacted form. Canonically, mitosis produces two daughter nuclei whose chromosome complement is identical to that of the mother cell. The synonym for this term is mitosis.
Why Is mitotic nuclear division Important in Cell Biology?
Mitotic nuclear division is essential for the accurate transmission of genetic material to daughter cells, and its failure leads to aneuploidy, chromosome instability, and cell death. Understanding this process is critical for cancer research, as many tumors exhibit mitotic defects and altered expression of mitotic genes. Moreover, the coordination between nuclear division and other cellular events, such as nuclear pore complex remodeling and membrane expansion, is a paradigm for studying organelle dynamics. Research in model organisms continues to reveal conserved and divergent mechanisms, informing both basic cell biology and potential therapeutic strategies.
• Ensures faithful chromosome segregation and genetic stability.
• Dysregulation causes aneuploidy and chromosome instability, hallmarks of cancer.
• Mitotic errors can activate the cGAS-STING innate immune pathway.
• Nuclear envelope and pore complex remodeling during mitosis are models for organelle dynamics.
• Mitotic memory influences gene expression and cell fate after division.
• Conserved mechanisms across eukaryotes allow use of diverse model organisms.
• Cytoplasmic division can occur independently of nuclear division, revealing modularity.
• SUMOylation regulates mitotic nuclear membrane expansion, linking post-translational modifications to division.
• Plant cytokinesis provides unique insights into cell plate formation.
• Understanding mitotic nuclear division aids development of anti-mitotic therapeutics.
What Happens During mitotic nuclear division?
Chromosome condensation and nuclear envelope breakdown
In simple terms: The cell packages its DNA into tight chromosomes and breaks down the nuclear envelope to prepare for division.
During early mitosis, chromosomal DNA is condensed into a highly compacted form, and the nuclear envelope begins to disassemble. In parallel, nuclear pore complexes are disassembled, a process that is tightly regulated and essential for proper mitotic progression. Studies in Caenorhabditis elegans have provided detailed insights into the steps of cell division, including chromosome condensation and nuclear envelope breakdown. The breakdown of the nuclear envelope allows spindle microtubules to access chromosomes, facilitating their segregation.
Nuclear pore complex disassembly and reassembly
In simple terms: The channels that control traffic in and out of the nucleus are taken apart and then put back together around the new nuclei.
Nuclear pore complexes (NPCs) are large protein assemblies that mediate nucleocytoplasmic transport. During mitosis, NPCs disassemble, and their components are dispersed; after chromosome segregation, NPCs reassemble around the daughter nuclei. This dynamic remodeling is crucial for nuclear function and has been studied in detail using biochemical and imaging approaches. Defects in NPC reassembly can lead to nuclear envelope defects and chromosome instability.
Nuclear membrane expansion and SUMOylation
In simple terms: The nuclear membrane grows and is modified by a small protein tag called SUMO to allow proper division.
The expansion of the mitotic nuclear membrane is regulated by SUMOylation, a post-translational modification that attaches SUMO proteins to target proteins. This modification is required for the efficient expansion of the nuclear membrane during mitosis, and its disruption leads to defects in nuclear division. The study by Siniossoglou (2023) highlights how SUMOylation acts as a molecular switch to coordinate membrane dynamics with mitotic progression.
Coordination with cytoplasmic division
In simple terms: The division of the nucleus is coordinated with the division of the rest of the cell, but they can sometimes occur independently.
Mitotic nuclear division is typically coupled with cytokinesis, the physical separation of the cytoplasm. However, recent work has shown that cytoplasmic division cycles can occur without the nucleus and without mitotic CDK/cyclin complexes, indicating that the two processes are modular. This finding challenges the traditional view that nuclear division is a prerequisite for cytoplasmic division and suggests that separate regulatory circuits exist. In plants, cytokinin-activated cell division involves distinct molecular mechanisms that coordinate nuclear and cellular division.
Mitotic memory and nuclear architecture
In simple terms: After division, daughter cells remember which genes were active, partly due to the way the nucleus is organized.
Nuclear architecture and the structural basis of mitotic memory are important for maintaining cell identity after division. The spatial organization of chromatin within the nucleus can influence gene expression and is propagated through mitosis, a phenomenon known as mitotic memory. This memory ensures that daughter cells retain the transcriptional programs of the mother cell, which is critical for development and tissue homeostasis.
Key Genes Involved in GO:0140014 mitotic nuclear division
The following genes and proteins are key players in mitotic nuclear division, as supported by the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CDK1 | Master kinase regulating mitotic entry and progression | Target for cell cycle studies and anti-mitotic drugs |
| Cyclin B | Regulatory subunit of CDK1 | Essential for mitotic CDK activity |
| SUMO | Post-translational modifier regulating nuclear membrane expansion | SUMOylation regulates mitotic nuclear membrane dynamics |
| Nuclear pore complex proteins (Nups) | Mediate nucleocytoplasmic transport; disassemble and reassemble during mitosis | Key to understanding NPC dynamics in division |
| DNAJA2 | Chaperone protein; deficiency causes aberrant mitosis | Links mitotic defects to cGAS-STING activation |
| cGAS | Cytosolic DNA sensor | Activated by chromosome instability from mitotic errors |
| STING | Adaptor in innate immune signaling | Mediates immune response to mitotic defects |
| Histones | Package DNA into chromatin; undergo condensation | Central to chromosome condensation |
| Condensins | Drive chromosome condensation | Required for mitotic chromosome compaction |
| Spindle tubulins | Form mitotic spindle for chromosome segregation | Target for spindle poisons |
| Kinetochore proteins | Attach chromosomes to spindle microtubules | Ensure accurate segregation |
| Aurora kinases | Regulate chromosome segregation and cytokinesis | Overexpressed in cancers |
| Plk1 | Polo-like kinase regulating mitotic progression | Potential therapeutic target |
| Cytokinin signaling components (plants) | Activate cell division in plants | Model for plant mitosis |
| SUMO proteases | Reverse SUMOylation | Regulate mitotic membrane dynamics |
| Nuclear lamins | Provide structural support to nuclear envelope | Disassemble and reassemble during mitosis |
| Ran GTPase | Regulates nucleocytoplasmic transport and spindle assembly | Critical for NPC reassembly |
How Is mitotic nuclear division Regulated?
Mitotic nuclear division is regulated by a complex network of kinases, phosphatases, and post-translational modifications. The master regulator CDK1-cyclin B drives entry into mitosis, while its inactivation is required for mitotic exit. SUMOylation regulates the expansion of the mitotic nuclear membrane, adding another layer of control. Nuclear pore complex disassembly and reassembly are regulated by phosphorylation and other modifications. In plants, cytokinin signaling activates cell division through a distinct molecular mechanism. Additionally, recent evidence shows that cytoplasmic division cycles can proceed without mitotic CDK/cyclin complexes, indicating the existence of alternative regulatory pathways.
mitotic nuclear division and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| DNAJA2 | Chromosome instability, cGAS-STING activation | Knockout in cancer cell lines |
| Aurora kinases | Cancer, mitotic defects | Point mutation and overexpression models |
| Plk1 | Cancer, mitotic arrest | Knockout and inhibitor studies |
| Lamins | Laminopathies, nuclear envelope defects | Knock-in of disease mutations |
| SUMO pathway | Mitotic membrane expansion defects | Knockout of SUMO enzymes |
Cancer and chromosome instability
Defects in mitotic nuclear division lead to chromosome instability (CIN), a hallmark of many cancers. For example, deficiency in DNAJA2 causes aberrant mitosis and chromosome instability, which activates the cGAS-STING innate immune pathway. This link between mitotic errors and immune activation suggests that targeting mitotic regulators could enhance anti-tumor immunity. Many cancers overexpress mitotic kinases such as Aurora kinases and Plk1, making them attractive therapeutic targets.
Developmental disorders and aneuploidy
Errors in mitotic nuclear division can result in aneuploidy, which is associated with developmental disorders and miscarriage. Proper chromosome segregation is essential for normal development, and mutations in genes encoding mitotic machinery can cause microcephaly and other congenital anomalies. Studies in model organisms such as C. elegans have elucidated the molecular basis of these defects.
Nuclear envelope-related diseases
Disruption of nuclear envelope and nuclear pore complex dynamics during mitosis can contribute to laminopathies and other nuclear envelope diseases. Mutations in lamins or NPC components can impair nuclear reassembly after mitosis, leading to nuclear deformities and cellular dysfunction. Understanding these processes may provide therapeutic avenues for rare genetic disorders.
From mitotic nuclear division-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate chromosome condensation? | Knockout cell lines followed by imaging |
| Does mutation Y cause mitotic delay? | Point mutation knock-in |
| How does protein Z localize during mitosis? | Tagged knock-in (e.g., GFP) |
| Does overexpression of gene W cause aneuploidy? | Overexpression cell lines |
| What is the role of SUMOylation in nuclear membrane expansion? | Knockout of SUMO enzymes |
| Can cytoplasmic division occur without nuclear division? | Microscopy in C. elegans embryos |
How to Study the mitotic nuclear division Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Dynamic localization and behavior of mitotic proteins | Studying chromosome segregation and nuclear envelope breakdown |
| CRISPR knockout | Loss-of-function phenotypes | Identifying essential mitotic genes |
| RNA-seq | Transcriptional changes during mitosis | Analyzing gene expression in synchronized cells |
| Proteomics | Protein abundance and modifications | Mapping mitotic phosphoproteome |
| ChIP-seq | Chromatin occupancy of mitotic proteins | Understanding mitotic memory |
| FRAP | Protein dynamics at nuclear envelope | Measuring NPC reassembly kinetics |
| Electron microscopy | Ultrastructure of mitotic nuclei | Visualizing nuclear envelope and NPCs |
Live-cell imaging
Live-cell imaging using fluorescently tagged proteins (e.g., GFP-tubulin, histone H2B-GFP) allows real-time visualization of chromosome condensation, spindle formation, and nuclear envelope dynamics. This method is essential for studying the temporal and spatial regulation of mitotic nuclear division.
RNA interference and CRISPR screens
High-throughput RNAi and CRISPR screens have identified numerous genes required for mitotic nuclear division. For example, a screen for chromosome instability identified DNAJA2 as a critical factor. These approaches enable unbiased discovery of novel regulators.
Proteomics and phosphoproteomics
Mass spectrometry-based proteomics can quantify changes in protein abundance and phosphorylation during mitosis. This is particularly useful for studying dynamic processes such as nuclear pore complex disassembly and reassembly.
Genome engineering with CRISPR
CRISPR-Cas9 technology allows precise knockout, point mutation, knock-in, and overexpression of genes involved in mitotic nuclear division. These models are invaluable for dissecting gene function and validating drug targets.
How CRISPR Can Be Used to Study GO:0140014 mitotic nuclear division
Knockout
CRISPR knockout of genes such as DNAJA2 has been used to demonstrate their role in mitotic nuclear division and chromosome stability. Knockout cell lines are valuable for studying loss-of-function phenotypes and for identifying synthetic lethal interactions.
Point Mutation
Point mutations can be introduced to model disease-associated variants or to study specific phosphorylation sites in mitotic regulators. For example, point mutations in Aurora kinases can alter their activity and cause mitotic defects.
Knock-in
Knock-in of tagged proteins (e.g., GFP, mCherry) allows visualization of endogenous proteins during mitosis. This approach is particularly useful for studying nuclear pore complex dynamics and nuclear envelope proteins.
Overexpression
Overexpression of mitotic genes such as Plk1 or Aurora kinases can induce mitotic defects and aneuploidy, providing models for cancer research. Overexpression models are also used to study gain-of-function mutations.
How EDITGENE Supports mitotic nuclear division Research
Researchers studying mitotic nuclear division-related genes often need to determine whether a candidate gene is causally involved in the process, and CRISPR-based models provide the most direct way to test this. By combining knockout, point mutation, knock-in, and overexpression strategies, it is possible to dissect gene function at multiple levels, from loss-of-function to gain-of-function, and to validate findings from high-throughput screens.
Contact EDITGENE today to design your custom CRISPR model for mitotic nuclear division research.
Frequently Asked Questions About mitotic nuclear division
What is mitotic nuclear division?
Mitotic nuclear division (GO:0140014) is the process by which a eukaryotic nucleus divides, producing two daughter nuclei with identical chromosome complements, as defined by the Gene Ontology.
What genes are involved in mitotic nuclear division?
Key genes include CDK1, Cyclin B, Aurora kinases, Plk1, DNAJA2, and nuclear pore complex proteins, among others.
What is the difference between mitosis and mitotic nuclear division?
Mitosis is a synonym for mitotic nuclear division (GO:0140014), referring to the same biological process.
How is mitotic nuclear division regulated?
It is regulated by CDK1-cyclin B, SUMOylation, and phosphorylation events that control chromosome condensation, nuclear envelope breakdown, and NPC disassembly.
What diseases are associated with defects in mitotic nuclear division?
Defects are linked to cancer, chromosome instability, aneuploidy, and developmental disorders.
What methods are used to study mitotic nuclear division?
Common methods include live-cell imaging, CRISPR screens, proteomics, and RNA-seq.
Can CRISPR be used to study mitotic nuclear division?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to dissect gene function in mitosis.
What is the role of nuclear pore complexes in mitosis?
Nuclear pore complexes disassemble during mitosis and reassemble around daughter nuclei, a process essential for nuclear function.
How does SUMOylation affect mitotic nuclear division?
SUMOylation regulates the expansion of the mitotic nuclear membrane, and its disruption leads to nuclear division defects.
What is mitotic memory?
Mitotic memory refers to the propagation of gene expression states through mitosis, influenced by nuclear architecture.
Conclusion
Mitotic nuclear division (GO:0140014) is a fundamental biological process that ensures faithful chromosome segregation and genetic stability. Its dysregulation is implicated in cancer, developmental disorders, and immune activation. Research using model organisms and CRISPR-based approaches continues to uncover the molecular mechanisms and regulatory networks that control this process. Understanding these mechanisms offers opportunities for therapeutic intervention and advances our knowledge of cell biology.
References
- 1. Yang W et al.. 2021. Molecular mechanism of cytokinin-activated cell division in Arabidopsis.. Science 371(6536):1350-1355 PMID: 33632892
- 2. Bakshi A et al.. 2023. Cytoplasmic division cycles without the nucleus and mitotic CDK/cyclin complexes.. Cell 186(21):4694-4709.e16 PMID: 37832525
- 3. Oegema K et al.. 2006. Cell division.. WormBook PMID: 18050484
- 4. Huang Y et al.. 2023. DNAJA2 deficiency activates cGAS-STING pathway via the induction of aberrant mitosis and chromosome instability.. Nat Commun 14(1):5246 PMID: 37640708
- 5. Soujanya M et al.. 2023. Nuclear architecture and the structural basis of mitotic memory.. Chromosome Res 31(1):8 PMID: 36725757
- 6. Kutay U et al.. 2021. Mitotic disassembly and reassembly of nuclear pore complexes.. Trends Cell Biol 31(12):1019-1033 PMID: 34294532
- 7. Siniossoglou S. 2023. Oiling the wheels of nuclear division: SUMOylation regulates the expansion of the mitotic nuclear membrane.. J Cell Biol 222(8) PMID: 37440179
- 8. Moldón A et al.. 2008. Promoter-driven splicing regulation in fission yeast.. Nature 455(7215):997-1000 PMID: 18815595
