GO:1901990 regulation of mitotic cell cycle phase transition: Cell Cycle Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1901990 (regulation of mitotic cell cycle phase transition) describes any process that modulates the frequency, rate or extent of transitions between mitotic cell cycle phases, including G1-S, G2-M and mitotic exit.
• Checkpoint kinases such as WEE1 and CDK1-centered networks set the timing of mitotic entry, while the spindle assembly checkpoint and APC/C control progression through mitosis and exit [1,5,7].
• Mitochondrial dynamics and metabolic state influence G1-S transition by regulating cyclin E accumulation, linking cell cycle control to cellular energetics.
• Caspases and transcription termination factors such as TTF2 participate in mitotic progression, showing that phase transition regulation extends beyond canonical CDK-cyclin modules [3,8].
• Dysregulation of mitotic phase transition control is a hallmark of cancer and is also implicated in developmental and degenerative conditions, making it a major therapeutic target [5,6].
• CRISPR knockout, point mutation, knock-in and overexpression models enable causal testing of candidate regulators of GO:1901990 in isogenic cell backgrounds.
Description
The mitotic cell cycle is a tightly ordered sequence of events in which a cell duplicates its genome and divides. The transitions between these phases, particularly G1-S, G2-M and mitotic exit, are not passive consequences of biosynthesis but are actively regulated by dedicated signaling modules. GO:1901990, regulation of mitotic cell cycle phase transition, captures the set of processes that modulate the frequency, rate or extent of these transitions. Understanding this ontology term is essential because errors in phase transition timing can lead to genome instability, aneuploidy and uncontrolled proliferation [1,5].
regulation of mitotic cell cycle phase transition At A Glance
| GO ID | GO:1901990 |
|---|---|
| GO term | regulation of mitotic cell cycle phase transition |
| Ontology | biological_process |
| Synonym | mitotic cell cycle control |
| Major function | Modulates the frequency, rate or extent of transitions between mitotic cell cycle phases |
| Related processes | G1-S transition, G2-M transition, mitotic exit, checkpoint signaling |
| Key regulators | CDK1, WEE1, MAD2, APC/C, cyclin E, caspases, TTF2 |
| Disease relevance | Cancer, aneuploidy, developmental disorders, degenerative conditions |
What Is GO:1901990?
GO:1901990 is a biological_process term defined as any process that modulates the frequency, rate or extent of mitotic cell cycle phase transition. In practice, it encompasses the checkpoint and regulatory activities that decide whether a cell proceeds from one mitotic phase to the next, rather than the mechanical execution of DNA replication or chromosome segregation itself.
Why Is regulation of mitotic cell cycle phase transition Important in Cell Biology?
Regulation of mitotic cell cycle phase transition is central to genome stability and cell fate. Checkpoint pathways that control G2-M and mitotic exit ensure that DNA replication and chromosome segregation are completed before division proceeds. When these controls fail, cells can enter mitosis with damaged DNA or exit prematurely, promoting aneuploidy and tumorigenesis [1,5]. Because many cancers depend on altered phase transition control, this GO term is a focal point for target discovery and drug development [5,6].
• Maintains order between DNA replication, mitosis and cytokinesis.
• Prevents premature mitotic entry through WEE1-mediated CDK1 inhibition.
• Coordinates spindle assembly checkpoint signaling with mitotic exit [1,5].
• Links metabolic and mitochondrial state to G1-S progression via cyclin E.
• Involves non-canonical regulators such as caspases and TTF2 [3,8].
• Its dysregulation is associated with cancer and chromosomal instability [5,6].
• Provides targets for checkpoint kinase inhibitors in oncology.
• Enables synthetic lethality strategies in cells with defective checkpoints [1,6].
• Supports stem cell and developmental studies where division timing is critical.
• Offers mechanistic readouts for CRISPR-based functional genomics [1,5].
What Happens During regulation of mitotic cell cycle phase transition?
G1-S transition control
In simple terms: The cell decides whether to copy its DNA.
The G1-S transition is regulated by factors that control cyclin E accumulation and entry into S phase. A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase, linking mitochondrial dynamics to cell cycle phase transition control.
G2-M transition and CDK1 activation
In simple terms: The cell checks that everything is ready before dividing.
The G2-M transition is governed by CDK1 activity, which is restrained by WEE1-mediated inhibitory phosphorylation. TRAP1 controls the G2-M transition through regulation of CDK1 and MAD2 expression and ubiquitination, showing that mitochondrial chaperones can modulate this checkpoint.
Spindle assembly checkpoint and mitotic exit
In simple terms: The cell waits until chromosomes are properly attached before finishing division.
Mitotic exit is controlled by checkpoints that monitor spindle attachment and chromosome segregation. Regulation of mitotic exit by cell cycle checkpoints has been dissected in Saccharomyces cerevisiae, revealing conserved principles for how checkpoint signaling delays exit until errors are corrected.
Proteolytic control of phase transitions
In simple terms: Targeted protein destruction drives the cell from one phase to the next.
Ubiquitin ligase complexes such as APC/C and SCF control the abundance of cell cycle regulators, and their interplay has been described as crashing waves of destruction that coordinate phase transitions.
Non-canonical regulators of mitosis
In simple terms: Other proteins beyond cyclins and CDKs also influence division timing.
Caspases contribute to cell cycle regulation at the mitotic phase, indicating that apoptotic machinery can also participate in mitotic control. The transcription termination factor TTF2 shows mutual regulation with the cell cycle, further expanding the regulatory network of mitotic phase transitions.
Key Genes Involved in GO:1901990 regulation of mitotic cell cycle phase transition
The following genes and proteins are experimentally implicated in the regulation of mitotic cell cycle phase transitions.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CDK1 | Catalytic subunit of the G2-M kinase complex | Central target for G2-M transition studies [5,7] |
| WEE1 | Inhibitory kinase that phosphorylates CDK1 | Regulates timing of mitotic entry |
| MAD2 | Spindle assembly checkpoint component | Controls mitotic exit fidelity |
| APC/C | Ubiquitin ligase controlling mitotic progression | Degrades securin and cyclins for exit |
| SCF(Skp2) | Ubiquitin ligase regulating G1-S effectors | Links proteolysis to phase transitions |
| CCNE1 | Cyclin E, partner of CDK2 at G1-S | Readout of G1-S transition control |
| TRAP1 | Mitochondrial chaperone modulating CDK1 and MAD2 | Connects metabolism to G2-M |
| TTF2 | Transcription termination factor with cell cycle roles | Mutual regulation with mitotic progression |
| CASP3 | Caspase contributing to mitotic regulation | Non-canonical mitotic control |
| CASP7 | Caspase implicated in mitotic phase regulation | Non-canonical mitotic control |
| CDC20 | Activator of APC/C during mitosis | Required for mitotic exit [1,6] |
| CDH1 | Activator of APC/C in G1 | Controls SCF(Skp2) and G1 progression |
| PLK1 | Polo-like kinase regulating mitotic entry and exit | Checkpoint and spindle function |
| AURKA | Aurora kinase A controlling centrosome maturation | G2-M transition regulation |
| AURKB | Aurora kinase B controlling chromosome segregation | Mitotic exit and cytokinesis |
| BUB1 | Spindle checkpoint kinase | Mitotic checkpoint signaling |
| BUBR1 | Spindle checkpoint kinase | Mitotic checkpoint signaling |
| CDC25 | Phosphatase activating CDK1 | G2-M transition control |
How Is regulation of mitotic cell cycle phase transition Regulated?
Regulation of mitotic cell cycle phase transition is itself controlled by checkpoint signaling, ubiquitin-mediated proteolysis and metabolic inputs. WEE1 phosphorylates and inhibits CDK1 to delay mitotic entry, while APC/C and SCF(Skp2) coordinate the ordered destruction of cell cycle regulators. Mitochondrial dynamics and chaperones such as TRAP1 modulate CDK1 and MAD2, linking cellular metabolism to G2-M control [2,5]. Transcription termination factor TTF2 shows mutual regulation with the cell cycle, indicating feedback between gene expression and phase transition machinery.
regulation of mitotic cell cycle phase transition and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| WEE1 | Cancer, premature mitotic entry | Knockout and point-mutation cell lines |
| TRAP1 | Cancer, G2-M dysregulation | Overexpression and knockout models |
| MAD2 | Aneuploidy, checkpoint defects | Knock-in reporter and knockout |
| APC/C subunits | Cancer, chromosomal instability | Knockout and degron knock-in |
| TTF2 | Cell cycle-related transcriptional defects | Knockout and tagged knock-in |
Cancer and genome instability
Loss of checkpoint control at mitotic phase transitions promotes aneuploidy and tumorigenesis. TRAP1-dependent regulation of CDK1 and MAD2 affects G2-M progression, and its dysregulation has been linked to cancer cell phenotypes. APC/C and SCF(Skp2) control of phase transitions is frequently altered in tumors, supporting the view that proteolytic timing is a cancer-relevant axis.
Therapeutic targeting of checkpoint kinases
Because WEE1 restrains CDK1 to prevent premature mitotic entry, WEE1 inhibitors are explored as a strategy to force cancer cells with defective checkpoints into mitotic catastrophe. Understanding GO:1901990 helps define which tumors may respond to such interventions [1,7].
Non-canonical regulators in disease biology
Caspases and TTF2 influence mitotic progression, suggesting that pathways traditionally associated with apoptosis or transcription can contribute to cell cycle-related disease phenotypes [3,8]. These findings broaden the set of candidate targets for experimental models of phase transition dysregulation [3,8].
From regulation of mitotic cell cycle phase transition-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate gene required for G2-M transition? | CRISPR knockout cell line [1,7] |
| Does a specific phosphorylation site control CDK1 timing? | Point-mutation knock-in |
| Where and when is a regulator expressed during mitosis? | Tagged knock-in reporter |
| Does overexpression accelerate G1-S transition? | Doxycycline-inducible overexpression |
| Which genes buffer checkpoint loss? | CRISPR library screening [1,6] |
| Does a mitochondrial regulator affect cyclin E buildup? | Knockout plus live imaging [2,5] |
How to Study the regulation of mitotic cell cycle phase transition Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Flow cytometry | DNA content and mitotic markers | Phase distribution after perturbation [1,5] |
| Live-cell imaging | Timing of G1-S and G2-M | Single-cell transition dynamics |
| Western blot | CDK1 phosphorylation and cyclin levels | Checkpoint activity readout [5,7] |
| Proteomics | Protein abundance and ubiquitination | APC/C and SCF substrate mapping |
| RNA-seq | Transcriptional changes across phases | Pathway discovery |
| CRISPR screening | Fitness and cell cycle phenotypes | Regulator identification [1,6] |
| Immunofluorescence | Spindle and chromosome morphology | Mitotic exit fidelity [1,5] |
Cell cycle profiling by flow cytometry
DNA content analysis and phospho-histone H3 staining allow researchers to quantify G1, S, G2 and M populations and detect shifts caused by perturbation of GO:1901990 regulators [1,5].
Live-cell imaging of phase transitions
Fluorescent reporters for cyclins and chromosome markers enable direct observation of G1-S and G2-M timing in single cells, as used to link mitochondrial state to cyclin E accumulation.
Proteomic and ubiquitin profiling
Mass spectrometry-based approaches can map the degradation of APC/C and SCF(Skp2) substrates, providing mechanistic insight into proteolytic control of phase transitions.
Transcriptomic and functional genomics
RNA-seq and CRISPR screens identify genes whose loss alters cell cycle progression, helping to assign function to candidates within the GO:1901990 network [1,8].
How CRISPR Can Be Used to Study GO:1901990 regulation of mitotic cell cycle phase transition
Knockout
CRISPR knockout of candidate regulators such as WEE1 or MAD2 allows direct testing of their requirement for normal phase transitions and checkpoint arrest [5,7].
Point Mutation
Introducing specific phosphorylation-site mutations in CDK1 or its regulators can dissect which residues control mitotic timing without deleting the entire protein.
Knock-in
Tagged knock-in of endogenous loci, for example TTF2 or cyclin E, enables tracking of protein localization and stability during phase transitions [2,8].
Overexpression
Inducible overexpression of cyclins or chaperones such as TRAP1 can test whether increased dosage accelerates or disrupts G1-S and G2-M progression [2,5].
How EDITGENE Supports regulation of mitotic cell cycle phase transition Research
Researchers studying regulation of mitotic cell cycle phase transition-related genes often need to determine whether a candidate gene is causally involved in phase progression, checkpoint control or disease-associated phenotypes. EDITGENE provides the CRISPR tools and cell models required to move from correlation to mechanism.
Contact EDITGENE today to design your custom CRISPR model for regulation of mitotic cell cycle phase transition research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDKN1B Knockout HEK293 Cell Line | EDJ-KQ766 | Human | 1027 | Details Get a Quote |
| PPP2R5C Knockout HEK293 Cell Line | EDJ-KQ856 | Human | 5527 | Details Get a Quote |
| MAD1L1 Knockout HEK293 Cell Line | EDJ-KQ2044 | Human | 8379 | Details Get a Quote |
| NEK11 Knockout HEK293 Cell Line | EDJ-KQ14410 | Human | 79858 | Details Get a Quote |
| TFAP4 Knockout HEK293 Cell Line | EDJ-KQ15710 | Human | 7023 | Details Get a Quote |
| XPC Knockout HEK293 Cell Line | EDJ-KQ16162 | Human | 7508 | Details Get a Quote |
| MAD1L1 Knockout A-549 Cell Line | EDJ-KQ22092 | Human | 8379 | Details Get a Quote |
| MAD1L1 Knockout HCT 116 Cell Line | EDJ-KQ22093 | Human | 8379 | Details Get a Quote |
| MAD1L1 Knockout HeLa Cell Line | EDJ-KQ22094 | Human | 8379 | Details Get a Quote |
| NEK11 Knockout A-549 Cell Line | EDJ-KQ44606 | Human | 79858 | Details Get a Quote |
| NEK11 Knockout HCT 116 Cell Line | EDJ-KQ44607 | Human | 79858 | Details Get a Quote |
| CDKN1B Knockout A-549 Cell Line | EDC08330 | Human | 1027 | Details Get a Quote |
| CDKN1B Knockout HCT 116 Cell Line | EDJ-KQ19461 | Human | 1027 | Details Get a Quote |
| CDKN1B Knockout HeLa Cell Line | EDJ-KQ19462 | Human | 1027 | Details Get a Quote |
| PPP2R5C Knockout A-549 Cell Line | EDJ-KQ19656 | Human | 5527 | Details Get a Quote |
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Frequently Asked Questions About regulation of mitotic cell cycle phase transition
What is GO:1901990?
GO:1901990 is the Gene Ontology biological process term for regulation of mitotic cell cycle phase transition, defined as any process that modulates the frequency, rate or extent of transitions between mitotic cell cycle phases.
What genes are involved in regulation of mitotic cell cycle phase transition?
Key genes include CDK1, WEE1, MAD2, APC/C subunits, CCNE1, TRAP1, TTF2 and caspases, all experimentally linked to phase transition control [1,2,3,5,6,7,8].
How is the G2-M transition regulated?
The G2-M transition is controlled by CDK1 activity, which is inhibited by WEE1 phosphorylation and modulated by factors such as TRAP1 that affect CDK1 and MAD2 [5,7].
What is the role of WEE1 in mitotic entry?
WEE1 phosphorylates CDK1 to delay mitotic entry, acting as a checkpoint kinase that prevents premature transition into mitosis.
How do mitochondria influence the G1-S transition?
A hyperfused mitochondrial state at G1-S regulates cyclin E buildup and entry into S phase, linking mitochondrial dynamics to cell cycle progression.
What is the spindle assembly checkpoint?
The spindle assembly checkpoint monitors chromosome attachment and delays mitotic exit until errors are corrected, a core component of phase transition regulation [1,5].
Can caspases regulate mitosis?
Yes, caspases have been shown to contribute to cell cycle regulation at the mitotic phase, indicating non-canonical roles beyond apoptosis.
How is TTF2 related to the cell cycle?
TTF2, a transcription termination factor, shows mutual regulation with the cell cycle, linking transcriptional termination to mitotic progression.
Why is regulation of mitotic cell cycle phase transition important in cancer?
Dysregulation of phase transition checkpoints promotes aneuploidy and uncontrolled proliferation, making these pathways attractive therapeutic targets [1,5,6].
How can CRISPR help study GO:1901990?
CRISPR knockout, point mutation, knock-in and overexpression models allow causal testing of candidate regulators of mitotic phase transitions in isogenic cell lines [1,5,7].
Conclusion
GO:1901990, regulation of mitotic cell cycle phase transition, defines the regulatory layer that governs when cells move between mitotic phases. Its components include checkpoint kinases, ubiquitin ligases, mitochondrial modulators and non-canonical factors such as caspases and TTF2 [1,2,3,5,6,7,8]. Because these processes are frequently altered in cancer and other diseases, precise CRISPR-based models are essential for mechanistic and translational research [1,5,6].
References
- 1. Matellán L et al.. 2020. Regulation of Mitotic Exit by Cell Cycle Checkpoints: Lessons From Saccharomyces cerevisiae.. Genes (Basel) 11(2) PMID: 32059558
- 2. Mitra K et al.. 2009. A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase.. Proc Natl Acad Sci U S A 106(29):11960-5 PMID: 19617534
- 3. Hashimoto T et al.. 2011. Contribution of caspase(s) to the cell cycle regulation at mitotic phase.. PLoS One 6(3):e18449 PMID: 21479177
- 5. Sisinni L et al.. 2017. TRAP1 controls cell cycle G2-M transition through the regulation of CDK1 and MAD2 expression/ubiquitination.. J Pathol 243(1):123-134 PMID: 28678347
- 6. Kurland JF et al.. 2004. Crashing waves of destruction: the cell cycle and APC(Cdh1) regulation of SCF(Skp2).. Cancer Cell 5(4):305-6 PMID: 15093536
- 7. McGowan CH et al.. 1995. Cell cycle regulation of human WEE1.. EMBO J 14(10):2166-75 PMID: 7774574
- 8. Hu Y et al.. 2025. Mutual regulation between cell cycle and transcription termination factor TTF2.. Sci China Life Sci 68(8):2348-2362 PMID: 40410652
