GO:0007088 regulation of mitotic nuclear division: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0007088 (regulation of mitotic nuclear division) is defined as any process that modulates the frequency, rate or extent of mitosis [QuickGO].
• Mitosis is controlled by reversible protein phosphorylation, nuclear transport factors, and nuclear envelope dynamics.
• Key regulators include AURKA, BORA, PLK1, CDK1, CCNB1, and MASTL (Greatwall kinase), which coordinate mitotic entry and progression.
• Disruption of mitotic regulation causes chromosome instability, aneuploidy, and diseases such as cancer and cGAS-STING-associated inflammation.
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal testing of mitotic regulators.
• Quantitative phosphoproteomics and live-cell imaging are core methods for studying mitotic regulation.
Description
Regulation of mitotic nuclear division (GO:0007088) encompasses all processes that modulate the frequency, rate, or extent of mitosis, the fundamental cell division program that ensures faithful chromosome segregation [QuickGO]. This regulation is essential for development, tissue homeostasis, and genome stability, and its dysregulation is a hallmark of cancer and other proliferative disorders. At the molecular level, mitosis is driven by reversible phosphorylation events, nuclear transport factors, and dynamic nuclear envelope remodeling. Quantitative phosphoproteomics has revealed widespread full phosphorylation site occupancy during mitosis, underscoring the density of regulatory inputs. Nuclear transport factors globally regulate mitotic progression by controlling the localization of key mitotic regulators such as Aurora-A and Greatwall kinase. The nuclear envelope, which disassembles and reassembles during mitosis, is also a critical node of regulation and quality control. Understanding GO:0007088 therefore requires integrating cell cycle signaling, nuclear dynamics, and disease-relevant mechanisms.
regulation of mitotic nuclear division At A Glance
| GO ID | GO:0007088 |
|---|---|
| GO term | regulation of mitotic nuclear division |
| Ontology | biological_process |
| Synonym | regulation of mitosis |
| Definition | Any process that modulates the frequency, rate or extent of mitosis. |
| Major function | Controls timing, speed, and fidelity of mitotic nuclear division. |
| Key molecular drivers | Reversible phosphorylation, nuclear transport factors, nuclear envelope dynamics. |
| Disease relevance | Cancer, chromosome instability, inflammation via cGAS-STING. |
| Research methods | Phosphoproteomics, live-cell imaging, CRISPR screens. |
What Is GO:0007088?
GO:0007088, regulation of mitotic nuclear division, is a biological process term defined as any process that modulates the frequency, rate or extent of mitosis [QuickGO]. In practice, this includes signaling pathways, protein modifications, and transport events that control when mitosis starts, how fast it proceeds, and whether it completes accurately.
Why Is regulation of mitotic nuclear division Important in Cell Biology?
Regulation of mitotic nuclear division is central to genome stability because errors in mitotic timing or execution lead to aneuploidy, DNA damage, and inflammatory signaling. Nuclear transport factors and mitotic kinases coordinate the localization and activity of effectors such as Aurora-A and Greatwall kinase, and their misregulation is linked to cancer. The nuclear envelope is not a passive barrier but an active participant in mitotic regulation and repair, with crosstalk between reassembly and repair pathways. Consequently, GO:0007088 is a high-value target for mechanistic studies and therapeutic development.
• Ensures faithful chromosome segregation and genome stability.
• Controls mitotic entry and progression through phosphorylation cascades.
• Regulates nuclear envelope disassembly and reassembly.
• Nuclear transport factors globally coordinate mitotic events.
• Dysregulation causes chromosome instability and aneuploidy.
• Links to cancer through Aurora-A and Greatwall kinase pathways.
• Activates innate immune signaling via cGAS-STING upon aberrant mitosis.
• Provides targets for anti-mitotic cancer therapies.
• Requires quantitative methods such as phosphoproteomics and imaging.
• Enables CRISPR-based causal dissection of mitotic regulators.
What Happens During regulation of mitotic nuclear division?
Mitotic entry and CDK1 activation
In simple terms: The cell decides to start mitosis by switching on a master kinase.
Mitotic entry is driven by activation of CDK1-cyclin B and its substrates, which trigger nuclear envelope breakdown and chromosome condensation. Quantitative phosphoproteomics shows that many mitotic phosphorylation sites are fully occupied, indicating robust and widespread regulatory phosphorylation during mitosis.
Greatwall kinase and mitotic progression
In simple terms: A kinase called Greatwall helps keep mitosis moving forward.
Greatwall kinase (MASTL) nuclear localization facilitates mitotic progression, and its regulation is important for timely mitosis. Nuclear transport factors control the localization of such regulators, linking nucleocytoplasmic trafficking to mitotic timing.
Aurora-A regulation and localization
In simple terms: Aurora-A must be in the right place at the right time to control mitosis.
Aurora-A nuclear localization is regulated and significant for its functions in cancer, and its proper localization is required for mitotic regulation. Nuclear transport factors globally regulate mitosis by controlling the distribution of Aurora-A and other effectors.
Nuclear envelope disassembly and reassembly
In simple terms: The nuclear envelope breaks down and rebuilds during mitosis, and this must be coordinated.
The nuclear envelope is a dynamic structure that disassembles and reassembles during mitosis, and its reassembly is coupled to repair pathways. Crosstalk between mitotic reassembly and repair of the nuclear envelope is critical for maintaining nuclear integrity.
Aberrant mitosis and chromosome instability
In simple terms: When mitosis goes wrong, chromosomes become unstable and can trigger inflammation.
DNAJA2 deficiency activates the cGAS-STING pathway via induction of aberrant mitosis and chromosome instability, demonstrating how mitotic errors feed into innate immune signaling. This links regulation of mitotic nuclear division directly to inflammatory and cancer-related outcomes.
Key Genes Involved in GO:0007088 regulation of mitotic nuclear division
The following genes and proteins are central to the regulation of mitotic nuclear division (GO:0007088), based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CDK1 | Master mitotic kinase | Controls mitotic entry and progression |
| CCNB1 | Cyclin B, CDK1 partner | Regulates mitotic timing |
| AURKA | Mitotic kinase | Nuclear localization linked to cancer |
| MASTL | Greatwall kinase | Nuclear localization facilitates mitotic progression |
| PLK1 | Polo-like kinase | Mitotic progression and phosphorylation |
| BORA | Aurora-A activator | Mitotic kinase regulation |
| TPX2 | Spindle assembly factor | Aurora-A pathway |
| DNAJA2 | Chaperone | Deficiency causes aberrant mitosis and cGAS-STING activation |
| RAN | Nuclear transport GTPase | Global regulation of mitosis |
| KPNB1 | Importin beta | Nuclear transport during mitosis |
| NUP98 | Nucleoporin | Nuclear envelope and transport |
| LMNB1 | Nuclear lamina | Nuclear envelope dynamics |
| EMD | Emerin | Nuclear envelope reassembly |
| SUN1 | LINC complex | Nuclear envelope integrity |
| NUP153 | Nucleoporin | Mitotic nuclear envelope remodeling |
| CHMP7 | ESCRT-III | Nuclear envelope repair |
| AURKB | Chromosomal passenger kinase | Mitotic regulation |
How Is regulation of mitotic nuclear division Regulated?
Regulation of mitotic nuclear division is controlled by reversible phosphorylation, nuclear transport, and nuclear envelope dynamics. CDK1-cyclin B and Aurora-A/PLK1 pathways drive mitotic entry and progression, while Greatwall kinase nuclear localization facilitates mitotic progression. Nuclear transport factors globally regulate mitosis by controlling the localization of these regulators. The nuclear envelope reassembly is coupled to repair pathways, ensuring nuclear integrity after mitosis.
regulation of mitotic nuclear division and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| AURKA | Cancer | Knockout and point-mutation models |
| DNAJA2 | Chromosome instability and cGAS-STING inflammation | Knockout models |
| MASTL | Mitotic progression defects | Knockout and knock-in models |
| LMNB1 | Nuclear envelope disorders | Knock-in and overexpression models |
| CDK1 | Cell cycle dysregulation | Point-mutation models |
Cancer and chromosome instability
Dysregulation of mitotic regulators such as Aurora-A is linked to cancer, and Aurora-A nuclear localization is significant for its oncogenic functions. Chromosome instability caused by aberrant mitosis can activate cGAS-STING signaling, linking mitotic errors to inflammation and tumorigenesis.
Inflammation via cGAS-STING
DNAJA2 deficiency activates the cGAS-STING pathway via induction of aberrant mitosis and chromosome instability, demonstrating a direct connection between mitotic regulation and innate immune activation.
Nuclear envelope-related disorders
Crosstalk between mitotic reassembly and repair of the nuclear envelope is essential; defects in this process can compromise nuclear integrity and contribute to disease.
From regulation of mitotic nuclear division-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a mitotic kinase required for proliferation? | CRISPR knockout |
| Does a specific phosphorylation site control mitotic timing? | Point mutation |
| Does a disease variant alter mitotic regulation? | Knock-in |
| Where does a regulator localize during mitosis? | Tagged knock-in |
| Does overexpression drive chromosome instability? | Overexpression |
| Which genes modulate mitotic progression? | CRISPR library screening |
How to Study the regulation of mitotic nuclear division Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Phosphoproteomics | Phosphorylation site occupancy | Mitotic signaling |
| Live-cell imaging | Mitotic progression and nuclear envelope dynamics | Real-time regulation |
| CRISPR knockout | Gene requirement | Causal testing |
| Point mutation | Site-specific function | Phosphorylation studies |
| Knock-in | Variant effects | Disease modeling |
| Overexpression | Gain-of-function effects | Chromosome instability |
| CRISPR library screening | Global regulators | Pathway discovery |
Quantitative phosphoproteomics
Phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis, providing a global view of regulatory phosphorylation.
Live-cell imaging
Imaging of nuclear envelope dynamics and mitotic progression allows real-time assessment of regulation.
CRISPR knockout and point-mutation models
Knockout of DNAJA2 causes aberrant mitosis and chromosome instability, demonstrating causal roles of specific genes. Point mutations can test phosphorylation site function.
Nuclear transport assays
Nuclear transport factors globally regulate mitosis, and their localization can be studied by imaging and fractionation.
How CRISPR Can Be Used to Study GO:0007088 regulation of mitotic nuclear division
Knockout
CRISPR knockout of DNAJA2 induces aberrant mitosis and chromosome instability, activating cGAS-STING, demonstrating the power of knockout models to reveal mitotic regulation. Knockout of MASTL can test its role in mitotic progression.
Point Mutation
Point mutations can be introduced to test specific phosphorylation sites identified by phosphoproteomics, such as those with full occupancy during mitosis.
Knock-in
Knock-in of disease-associated variants in genes such as LMNB1 or AURKA allows modeling of nuclear envelope and mitotic defects.
Overexpression
Overexpression of mitotic regulators like Aurora-A can drive chromosome instability and cancer-related phenotypes.
How EDITGENE Supports regulation of mitotic nuclear division Research
Researchers studying regulation of mitotic nuclear division-related genes often need to determine whether a candidate gene is causally involved in mitotic timing, chromosome segregation, or disease-associated phenotypes. EDITGENE provides end-to-end CRISPR services to generate precisely engineered cell models for such studies.
Contact EDITGENE today to design your custom CRISPR model for regulation of mitotic nuclear division research.
Frequently Asked Questions About regulation of mitotic nuclear division
What is GO:0007088?
GO:0007088 is the Gene Ontology term for regulation of mitotic nuclear division, defined as any process that modulates the frequency, rate or extent of mitosis [QuickGO].
What genes are involved in regulation of mitotic nuclear division?
Key genes include CDK1, CCNB1, AURKA, MASTL, PLK1, and DNAJA2, among others.
How is mitosis regulated?
Mitosis is regulated by reversible phosphorylation, nuclear transport factors, and nuclear envelope dynamics.
What is the role of Aurora-A in mitosis?
Aurora-A nuclear localization is regulated and significant for its functions in cancer and mitotic regulation.
What is Greatwall kinase?
Greatwall kinase (MASTL) nuclear localization facilitates mitotic progression.
How does aberrant mitosis cause inflammation?
Aberrant mitosis and chromosome instability can activate the cGAS-STING pathway, as shown in DNAJA2 deficiency.
What methods study mitotic regulation?
Quantitative phosphoproteomics, live-cell imaging, and CRISPR screens are commonly used.
What diseases are linked to mitotic regulation?
Cancer and inflammatory conditions linked to chromosome instability are associated with dysregulated mitosis.
What is the nuclear envelope's role in mitosis?
The nuclear envelope disassembles and reassembles during mitosis, with crosstalk to repair pathways.
How can CRISPR help study mitotic regulation?
CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of mitotic regulators.
Conclusion
Regulation of mitotic nuclear division (GO:0007088) is a central biological process that ensures genome stability through coordinated phosphorylation, nuclear transport, and nuclear envelope dynamics. Its dysregulation is linked to cancer and inflammation, making it a key area for mechanistic and therapeutic research. CRISPR-based models and quantitative methods provide powerful tools to dissect this process.
References
- 2. Olsen JV et al.. 2010. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.. Sci Signal 3(104):ra3 PMID: 20068231
- 3. 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
- 4. Forbes DJ et al.. 2015. Nuclear transport factors: global regulation of mitosis.. Curr Opin Cell Biol 35:78-90 PMID: 25982429
- 5. Kono Y et al.. 2024. Crosstalk between mitotic reassembly and repair of the nuclear envelope.. Nucleus 15(1):2352203 PMID: 38780365
- 6. Wang P et al.. 2013. Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression.. J Cell Biol 202(2):277-93 PMID: 23857770
- 7. Naso FD et al.. 2021. Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer.. Oncogene 40(23):3917-3928 PMID: 33981003
- 8. Hetzer MW. 2010. The nuclear envelope.. Cold Spring Harb Perspect Biol 2(3):a000539 PMID: 20300205
